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Science 22 May 1998:
Vol. 280. no. 5367, pp. 1262 - 1265
DOI: 10.1126/science.280.5367.1262
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Reports

Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase

Montserrat Camps, * Anthony Nichols, * Corine Gillieron, * Bruno Antonsson, * Marco Muda, dagger Christian Chabert, * Ursula Boschert, * Steve Arkinstall *ddagger

MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 mutant D319N nor c-Jun amino-terminal kinase-stress-activated protein kinase (JNK/SAPK) or p38 MAP kinases bound MKP-3 or caused its catalytic activation. These kinases were also resistant to enzymatic inactivation by MKP-3. Another homologous but nonselective phosphatase, MKP-4, bound and was activated by ERK2, JNK/SAPK, and p38 MAP kinases. Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems.

Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development S.A., CH-1228 Plan-les-Ouates, Geneva, Switzerland.
*   Present address: Serono Pharmaceutical Research Institute, CH-1228, Plan-les-Ouates, Geneva, Switzerland.

dagger    Present Address: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.

ddagger    To whom correspondence should be addressed. E-mail: steve.arkinstall{at}serono.com

Signal transduction pathways that lead to activation of MAP kinases control many diverse and essential functions in yeast, worms, flies, and mammals. Extracellular signal-regulated kinase-1 (ERK1) and ERK2 exemplify one class of MAP kinase that undergoes activation by a range of stimuli including growth factors, cytokines, cell adhesion, tumor-promoting phorbol esters, and oncogenes (1). Specific functions assigned to ERK activity include chemotaxis, neuronal differentiation, and synaptic changes underlying memory and learning, as well as cellular mitogenesis and oncogenic transformation (1, 2).

Full activation of ERK requires phosphorylation of threonine and tyrosine residues by a class of MAP kinase/ERK kinase (MEK) exemplified by MEK-1 (1, 3). Conversely, an emerging family of dual-specificity phosphatases that act on both phosphotyrosine and phosphothreonine reverse this process and also appear to be critical regulators of MAP kinase activity. CL100/3CH134 or MAP kinase phosphatase-1 (MKP-1) is the archetypal member of this gene family and has high substrate specificity for MAP kinases (4). Up to nine other mammalian dual-specificity phosphatases have been identified, and several of these are under tight transcriptional control and display distinct tissue, cell, and subcellular expression patterns (5, 6). MKP-3 appears exceptional in that it specifically inactivates ERK as compared with c-Jun NH2-terminal kinases/stress-activated protein kinases (JNK/SAPK) or p38 MAP kinases (7). We now show that ERK, but not other MAP kinases, cause substrate-triggered activation of MKP-3.

We purified various MKP-3 deletion mutants expressed in Escherichia coli and found that the NH2-terminal noncatalytic domain (amino acids 1 to 221) binds tightly to its target MAP kinases p44 ERK1 and p42 ERK2 (8). Binding to purified ERK2 (9) stimulates p-nitrophenyl phosphate (p-NPP) phosphatase activity of full-length MKP-3 by up to 30-fold (Fig. 1A) (10). Both glutathione-S-transferase (GST)-ERK2 and ERK2 caused similar activation of either the fusion protein GST-MKP-3, His-tagged MKP-3, or free MKP-3 (11). Activation of MKP-3 was dose-dependent and saturable with half-maximal effect detected in the presence of 5 µg (~0.5 µM) of ERK2 (Fig. 1B). No increase in phosphatase activity was detected upon binding of ERK2 to a catalytically inactive MKP3 mutant in which Cys-293 is substituted by Ser (C293S) (Fig. 2, A and B). Consistent with ERK2 binding to MKP-3 through its NH2-terminus (8), the purified MKP-3Delta N catalytic core (residues 153 to 381) was insensitive to enzymatic activation by ERK2 (Fig. 2C). Moreover, enzymatic activation of full-length MKP-3 by ERK2 was inhibited (half-maximal inhibition at ~ 1 µM) in the presence of the purified noncatalytic NH2-terminus of MKP-3 (MKP-3Delta C; amino acids 1 to 221) (Fig. 2D). Addition of the catalytically inactive MKP-3 mutant C293S also inhibited ERK2-dependent activation of wild-type (WT) MKP-3 (Fig. 2D). Because both MKP-3Delta C and MKP-3 C293S bind ERK2 tightly (8), this inhibition probably reflects competition for ERK2 binding to WT MKP-3.

Fig. 1. Activation of MKP-3 by ERK2. Phosphatase activity was measured as p-NPP hydrolysis at 25°C monitored at an absorbance of 405 nm (A405) (10). Full-length GST-MKP-3 and GST-ERK2 were expressed in E. coli and purified on glutathione-Sepharose. ERK2 was further purified by ion-exchange chromatography (9, 10). (A) Time-dependent hydrolysis of p-NPP by 5 µg of GST-MKP-3 either alone (0 µg) or in the presence of the indicated amounts of ERK2. Linear reaction rates are indicated by lines of best fit. Ten micrograms of ERK2 stimulated phosphatase activity by 25.5-fold. (B) Activation of the indicated amounts of GST-MKP-3 by purified ERK2. Incubations were for 30 min. Maximal ERK2-dependent activation with 10 µg of MKP-3 was 35 times the basal phosphatase activity. Data points are the mean of duplicate determinations and are representative of three independent experiments. [View Larger Version of this Image (21K GIF file)]

Fig. 2. Requirement of the MKP-3 catalytic Cys-293 and binding to the MKP-3 NH2-terminus for ERK2-dependent activation. Phosphatase activity was measured as described (Fig. 1). Incubations were performed with the indicated concentrations of (A) WT GST-MKP-3, (B) inactive mutant GST-MKP-3 C293S, or (C) NH2-terminally truncated GST-MKP-3Delta N (amino acids 153 to 381) in the absence (circle ) or presence (bullet ) of ERK2 (5 µg). (D) Inhibition of ERK2-dependent activation of MKP-3 by the indicated concentrations of mutant inactive GST-MKP-3 (C293S) (downtriangle ), the MKP-3 NH2-terminus GST-MKP-3Delta C (amino acids 1 to 221) (bullet ), or GST protein (circle ) incubated in the presence of GST-MKP-3 (2.5 µg) and ERK2 (2.5 µg). (blacksquare ) MKP-3 activity in the absence of ERK2. Data represent the mean of two identical experiments each performed in triplicate. [View Larger Version of this Image (26K GIF file)]

To examine whether ERK2 enzymatic activity is necessary for binding and catalytic activation of MKP-3, we purified an inactive GST-ERK2 mutant in which Lys-52 is changed to Ala (K52A) (9). Like WT MAP kinase, ERK2 K52A bound (12) to MKP-3 and increased phosphatase activity (Fig. 3, A and B). GST-ERK2 K52A did not phosphorylate myelin basic protein (MBP) (Fig. 3C), demonstrating that MKP-3 activation is independent of MAP kinase activity.


Fig. 3. ERK-specific binding and activation of MKP-3. (A) GST- ERK2, GST-ERK2 K52A,GST-SAPKalpha (JNK2), GST-SAPKbeta (JNK3), and GST-p38 MAP kinases immobilized on glutathione-Sepharose beads (9) were incubated with free His-tagged MKP-3 (10). After extensive washing, binding was assessed by protein immunoblotting. Bound MKP-3 was detected with a polyclonal antibody to MKP-3. Binding of antibody to rabbit immunoglobulin G coupled to peroxidase was detected by chemilumines-cence. His-tagged MKP-3 (5 ng) was used as a positive control. (B) Hydrolysis of p-NPP by MKP-3 in the presence of theindicated concentrations of eluted GST-ERK2 (circle ), catalytically inactive GST-ERK2 K52A (bullet ), GST-SAPKalpha (JNK2) (blackdowntriangle ), GST- SAPKbeta (JNK3) (square ), or GST-p38 MAP kinase (triangle ). (C) Substrate phosphorylation by MAP kinase proteins used in (B). MAP kinases were incubated in kinase buffer in the presence of [gamma -32P]ATP (9) together with either MBP (GST-ERK2 or GST-ERK2 K52A), GST-c-Jun (1-79) [GST-SAPKalpha (JNK2) or GST-SAPKbeta (JNK3)], or GST-ATF-2 (19-96) (GST-p38) before separation by SDS-polyacrylamide gel electrophoresis (15% gel), drying, and autoradiography. These experiments were performed three times with identical results. [View Larger Versions of these Images (40 + 19 + 19K GIF file)]

In both in vitro and in cell transfection studies, low concentrations of MKP-3 inactivate ERK but not JNK/SAPK or p38 MAP kinases (7), which also fail to bind directly to MKP-3 (Fig. 3A). Furthermore, activation of MKP-3 appears to be limited strictly to the ERK class of MAP kinase because neither SAPKalpha (JNK2), SAPKbeta (JNK3), or p38 induced an increase in phosphatase activity (Fig. 3B). All MAP kinases tested appeared to be folded correctly and to be active as indicated by phosphorylation of an appropriate substrate protein (9) (Fig. 3C) and activation of the MKP-3 homolog, MKP-4 (see below).

Genetic analysis in Drosophila suggests that the ERK MAP kinase rolled is a critical component of the Sevenless signal transduction pathway (13). A dominant gain-of-function mutation of the rolled MAP kinase gene, termed Sevenmaker, (rlsevenmaker) contains a single amino acid substitution of Asn for Asp-334 (D334N) and activates several developmental pathways (14). The analogous mutant of mammalian ERK2 is also more sensitive to activation in vivo and appears to be resistant to inactivation by dual-specificity phosphatases in transfected cells (15). We tested the mammalian ERK2 Sevenmaker D319N mutation and found that it bound MKP-3 only weakly (Fig. 4A). Moreover, ERK2 D319N stimulated MKP-3 phosphatase activity only 10 to 15% as well as WT MAP kinase (Fig. 4B). This deficiency in its ability to trigger MKP-3 activation does not reflect misfolding of the purified Sevenmaker protein, which phosphorylated MBP as effectively as WT ERK2 (Fig. 4C). This observation suggests that one critical consequence of the ERK2 D319N mutation is an inability to bind and trigger catalytic activation of MKP-3.


Fig. 4. Deficient binding and activation of MKP-3 by the ERK2 D319N Sevenmaker mutation. (A) GST-ERK2 or GST ERK2 D319N immobilized on glutathione-Sepharose beads (9) were incubated with His-tagged MKP-3, and binding was assessed as described (Fig. 3). His-tagged MKP-3 (7 ng) was used as a positive control. (B) Hydrolysis of p-NPP by MKP-3 in the presence of the indicated concentrations of GST-ERK2 (bullet ), GST-ERK2 D319N Sevenmaker (circle ), or GST alone (triangle ). (C) MBP phosphorylation by WT GST-ERK2 and Sevenmaker ERK2 D319N after incubation in kinase buffer in the presence of [gamma -32P]ATP (9). Proteins were separated and detected as described (Fig. 3). [View Larger Versions of these Images (45 + 17 + 29K GIF file)]

To examine whether this deficiency is paralleled by resistance to inactivation, we next measured MKP-3-dependent inhibition of WT and Sevenmaker ERK2 activated in vitro by the constitutive MAP kinase kinase MEK1 in which Ser-217 and Ser-221 are changed to glutamate (S217E and S221E) (16). MKP-3 potently inactivated WT ERK2, but more than 10 times as much MKP-3 was required to inhibit MBP phosphorylation by the ERK2 Sevenmaker mutant (Fig. 5, A and B). Similar observations were also made in mammalian cells transfected with WT ERK2 or ERK2 D319N together with a range of MKP-3 plasmid concentrations (17). Epidermal growth factor (EGF)-stimulated ERK2 D319N activation was inhibited only partially at levels of MKP-3 expression that abolished WT ERK2 activity (Fig. 6A). Taken together, these observations indicate that the Sevenmaker mutation interferes with binding to MKP-3 and, as a consequence, prevents a substrate-dependent increase in MKP-3 phosphatase activity, resulting in less-effective ERK2 inactivation. Impaired catalytic activation of MKP-3 may thereby underlie the gain-of-function phenotype of the ERK2 Sevenmaker mutation.

Fig. 5. Resistance of ERK2 D319N Sevenmaker to inactivation by MKP-3. Wild-type ERK2 (A and C) or ERK2 D319N (B) (0.5 µg) were incubated in vitro in the absence (lane 1) or presence (all other lanes) of 0.1 µg of constitutively active MEK1 (S217E S221E) (16) and with the indicated concentrations (0.01 to 10 µg) of full-length MKP-3 (A and B) or MKP-3Delta N (amino acids 153 to 381) (C). Figure shows autoradiograms of MBP phosphorylation by activated MAP kinases. Experiments were repeated three times with identical results. [View Larger Version of this Image (71K GIF file)]


Fig. 6. Inactivation of ERKD319N and WT ERK MAP kinases by MKP-3 or MKP-3Delta N in mammalian cells. COS-7 cells were transfected with either Myc-ERK2 D319N (A), WT Myc-ERK2 (B), or WT hemagglutinin A (HA)-ERK1 (C) together with the indicated concentrations of MKP-3 or MKP-3Delta N plasmid (17). After culture for 40 hours, cells were incubated for 2 hours in serum-free medium and either untreated (lane 1) or stimulated with EGF (10 nM) for 10 min (all other lanes). Subsequent MAP kinase immunoprecipitation, immune complex assays, and protein immunoblotting were performed as described (17). (A) ERK2 D319N is resistant to inactivation by MKP-3 in COS-7 cells. (Top) Autoradiographs of MBP phosphorylation by EGF-stimulated ERK2 or ERK2 D319N in the absence and presence of various amounts of coexpressed WT MKP-3. (Middle) Protein immunoblotting of corresponding immunoprecipitated ERK2 or ERK2 D319N. (Bottom) Levels of immunodetected MKP-3 in crude cell lysates. (B and C) ERK2 and ERK1 are resistant to inactivation by MKP-3Delta N. (Top) Autoradiographs of MBP phosphorylation by EGF-stimulated ERK2 (B) or ERK1 (C) in the absence or presence of MKP-3 or MKP-3Delta N as indicated. (Bottom) Protein immunoblotting of corresponding immunoprecipitated ERK2 (B) or ERK1 (C). In (B) and (C), indistinguishable levels of MKP-3 and MKP-3Delta N protein expression were detected for each corresponding plasmid concentration (11). Each experiment was performed twice with identical results. [View Larger Versions of these Images (50 + 33 + 40K GIF file)]

These observations suggest that mutations in MKP-3 that interfere with binding to ERK2 may also lead to MAP kinase resistance to inactivation. Consistent with this prediction, the purified catalytic core of MKP-3 (MKP-3Delta N; amino acids 153 to 381), which failed to bind ERK2 (8) or to undergo enzymatic activation by this MAP kinase (Fig. 2C), was ~1/10th as effective at reversing in vitro ERK2 activation by MEK-1 (S217E and S221E) (Fig. 5C). Also in mammalian cells (17), EGF-stimulated ERK2 activity was resistant to inactivation by MKP-3Delta N as compared with WT MKP-3 (Fig. 6B). As anticipated by binding of ERK1 to the NH2-terminus of MKP-3 (8), this closely related MAP kinase isoform was also resistant to inactivation by MKP-3Delta N in mammalian cells (Fig. 6C).

MKP-4 is a homologous dual-specificity phosphatase displaying low sequence identity with MKP-3 within its NH2-terminus. MKP-4 also appears functionally distinct from MKP-3 in that it displays relatively nonselective inactivation of ERK, JNK/SAPK, and p38 MAP kinases (6). Consistent with these differences and unlike MKP-3, MKP-4 bound ERK2, SAPKbeta (JNK3), and p38 and underwent dose-dependent p-NPP phosphatase activation by all three MAP kinase isoforms (Fig. 7, A and B). As with MKP-3, ERK2 D319N failed to bind or trigger catalytic activation of MKP-4 (11).


Fig. 7. MKP-4 binding and activation by ERK2, SAPKbeta (JNK3), and p38 MAP kinases. (A) COS-7 cells transfected with Myc-MKP-3 or Myc-MKP-4 (17) were lysed and incubated with immobilized MAP kinases as described (Fig. 3). MKP-3 and MKP-4 bound to GST-ERK2, GST-SAPKbeta (JNK3), and GST-p38 was measured by protein immunoblotting with monoclonal antibody to Myc (12). The control represents crude lysates from cells transfected as indicated. (B) Purified MKP-4 p-NPP phosphatase activity measured in the presence of the indicated concentrations of GST-ERK2 (bullet ), GST-SAPKbeta (JNK3) (blacktriangle ), GST-p38 MAP (circle ), or GST (triangle ). Data points are the mean of duplicate determinations and are representative of three independent experiments. [View Larger Versions of these Images (27 + 18K GIF file)]

Transcription of many dual-specificity phosphatases is regulated in response to growth and differentiation factors or cell stresses (4-6). Our results indicate that their catalytic activation through binding substrate MAP kinases may represent a secondary posttranslational mechanism for control. ERK-specific MKP-3 activation through binding of its noncatalytic NH2-terminus may indicate that sequence diversity of dual-specificity phosphatases within this region (6) enables their selective activation through binding different repertoires of substrate MAP kinases. This may provide a mechanism for targeted inactivation of selected MAP kinases.

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  9. ERK2, ERK2 K52A, ERK2 D319N, SAPKalpha (JNK2), SAPKbeta (JNK3), and p38 MAP kinases were produced in E. coli as GST fusion proteins and purified by binding to glutathione-Sepharose. All MAP kinases were >90% pure. Bead-immobilized MAP kinases were used for binding MKP-3 (13); for phosphatase activation (10) MAP kinases were eluted with 50 mM tris (pH 8.0) containing 5 mM glutathione. For some experiments GST-ERK2 and GST-MKP-3 were cleaved from their GST fusion protein by incubation with thrombin and further purified by fast protein liquid chromatography with Mono Q Sepharose followed by dialysis against 20 mM tris (pH 7.5) containing 0.5 mM EGTA, 5 mM MgCl2, and 2 mM dithiothreitol (DTT). This ERK2 was >95% pure. MAP kinase phosphorylation assays were done with [gamma -32P]ATP (adenosine 5'-triphosphate) as described (6, 8).
  10. MKP-3, catalytically inactive MKP-3 (C293S), MKP-3Delta N (amino acids 153 to 381), MKP-3Delta C (amino acids 1 to 221), and MKP-4 subcloned into pGEX 4T3 (6, 8) were expressed in E. coli by induction with 100 µM isopropyl-beta -D-thiogalactopyranoside and growth at 20°C. GST fusion proteins were purified with glutathione-Sepharose (Pharmacia LKB Biotechnology) and eluted in 50 mM tris (pH 8.0) containing 5 mM glutathione. His-MKP-3 was expressed under identical conditions and purified with Ni-agarose and eluted with 300 mM imidazole. All proteins were >90% pure. Phosphatase activity was measured in 96-well plates in 200 µl of 50 mM imidazole (pH 7.5) containing 5 mM DTT, 20 mM p-NPP, and the indicated concentrations of MKP-3 and various purified MAP kinases (9). Reaction rates were measured at 405 nm in a microplate reader (Molecular Devices).
  11. M. Camps, C. Gillieron, S. Arkinstall, unpublished data.
  12. His-tagged MKP-3 (0.1 µg) was incubated with MAP kinases immobilized on beads (3 µg) in 20 mM tris-acetate (pH 7.0) containing 1% Triton X-100, 50 mM NaF, 1 mM EDTA, 1 mM EGTA, 1 mM sodium vanadate, 0.27 M sucrose, 5 mM sodium pyrophosphate, 10 mM beta -glycerophosphate, and 0.1% beta -mercaptoethanol together with a cocktail of protease inhibitors overnight at 4°C with mixing. Beads were washed four times in 10 mM tris (pH 7.4), and bound MKP-3 was analyzed by protein immunoblotting with a polyclonal antibody directed to the peptide VVLYDENSSDWNENTGGE (amino acids 95 to 112). In some experiments COS-7 cells were transfected with pMT-SM-Myc-MKP-3 or pMT-SM-Myc-MKP-4 (6, 11), and binding to immobilized MAP kinases (3 µg) was measured under identical conditions except that MKP-3 and MKP-4 protein was detected with monoclonal antibody to the Myc epitope (8). Abbreviations for the amino acid residues are as follows: D, Asp; E, Glu; G, Gly; L, Leu; N, Asn; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
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  16. Constitutively active rabbit MEK1 EE (S217E and S221E) was purified and used to activate ERK as described (8).
  17. COS-7 cells were transfected with pEXV3-Myc-ERK2, pEXV3-Myc-ERK2 D319N, or pcDNA1-HA-ERK1 together with various concentrations of pMT-SM-MKP-3 or pMT-SM-MKP-3Delta N followed by EGF stimulation, MAP kinase immunoprecipitation, and immune complex assays were performed exactly as described (6, 8). pMT-SM-MKP-3Delta N (amino acids 153 to 381) was constructed by digesting pMT-SM-MKP-3 (6) with Pst I-Xba I followed by ligation with a double-stranded oligonucleotide containing an ATG codon following a Kozak consensus.
  18. We thank J. R. Woodgett (Ontario Cancer Institute, Canada) for pMT2-HA-SAPKbeta (JNK3) and pGEX-SAPKalpha (JNK2); E. Bettini (Glaxo Wellcome, Verona, Italy) for pGEX-c-Jun-(1-79); S. Stimpson (Glaxo Wellcome, Research Triangle Park, NC) for pGEX-p38; and C. J. Marshall (Chester Beatty Labs, ICR, London, UK) for pGEX-2T/ERK2, pGEX-2T/ERK2 D319N (Sevenmaker), pGEX-2T/ERK2 K52A, pGEX-3X/MEK1 (S217E, S221E), pEXV3-Myc-ERK2, pEXV3-Myc-ERK2 D319N, and rabbit antibody 122 specific for ERK2.
24 December 1997; accepted 9 April 1998


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Physiol Genomics 30, 242-252
   Abstract »    Full Text »    PDF »
Regulation of innate immunity by MAPK dual-specificity phosphatases: knockout models reveal new tricks of old genes.
K. Salojin and T. Oravecz (2007)
J. Leukoc. Biol. 81, 860-869
   Abstract »    Full Text »    PDF »
Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development.
C. Li, D. A. Scott, E. Hatch, X. Tian, and S. L. Mansour (2007)
Development 134, 167-176
   Abstract »    Full Text »    PDF »
Mapping ERK2-MKP3 Binding Interfaces by Hydrogen/Deuterium Exchange Mass Spectrometry.
B. Zhou, J. Zhang, S. Liu, S. Reddy, F. Wang, and Z.-Y. Zhang (2006)
J. Biol. Chem. 281, 38834-38844
   Abstract »    Full Text »    PDF »
DUSP Meet Immunology: Dual Specificity MAPK Phosphatases in Control of the Inflammatory Response.
R. Lang, M. Hammer, and J. Mages (2006)
J. Immunol. 177, 7497-7504
   Abstract »    Full Text »    PDF »
Diverse physiological functions for dual-specificity MAP kinase phosphatases.
R. J. Dickinson and S. M. Keyse (2006)
J. Cell Sci. 119, 4607-4615
   Abstract »    Full Text »    PDF »
Oxidative stress and mitogen-activated protein kinase phosphorylation mediate ammonia-induced cell swelling and glutamate uptake inhibition in cultured astrocytes..
A. R. Jayakumar, K. S. Panickar, Ch. R. K. Murthy, and M. D. Norenberg (2006)
J. Neurosci. 26, 4774-4784
   Abstract »    Full Text »    PDF »
Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heart.
A. K. Olson, K. N. Protheroe, J. L. Segar, and T. D. Scholz (2006)
Am J Physiol Heart Circ Physiol 290, H1587-H1595
   Abstract »    Full Text »    PDF »
Cooperation of ERK and SCFSkp2 for MKP-1 Destruction Provides a Positive Feedback Regulation of Proliferating Signaling.
Y.-W. Lin and J.-L. Yang (2006)
J. Biol. Chem. 281, 915-926
   Abstract »    Full Text »    PDF »
Rapid Estrogenic Regulation of Extracellular Signal- Regulated Kinase 1/2 Signaling in Cerebellar Granule Cells Involves a G Protein- and Protein Kinase A-Dependent Mechanism and Intracellular Activation of Protein Phosphatase 2A.
S. M. Belcher, H. H. Le, L. Spurling, and J. K. Wong (2005)
Endocrinology 146, 5397-5406
   Abstract »    Full Text »    PDF »
Catalytic Activation of the Plant MAPK Phosphatase NtMKP1 by Its Physiological Substrate Salicylic Acid-induced Protein Kinase but Not by Calmodulins.
S. Katou, E. Karita, H. Yamakawa, S. Seo, I. Mitsuhara, K. Kuchitsu, and Y. Ohashi (2005)
J. Biol. Chem. 280, 39569-39581
   Abstract »    Full Text »    PDF »
ERK2 Shows a Restrictive and Locally Selective Mechanism of Recognition by Its Tyrosine Phosphatase Inactivators Not Shared by Its Activator MEK1.
C. Tarrega, P. Rios, R. Cejudo-Marin, C. Blanco-Aparicio, L. van den Berk, J. Schepens, W. Hendriks, L. Tabernero, and R. Pulido (2005)
J. Biol. Chem. 280, 37885-37894
   Abstract »    Full Text »    PDF »
Dual Specificity MAPK Phosphatase 3 Activates PEPCK Gene Transcription and Increases Gluconeogenesis in Rat Hepatoma Cells.
H. Xu, Q. Yang, M. Shen, X. Huang, M. Dembski, R. Gimeno, L. A. Tartaglia, R. Kapeller, and Z. Wu (2005)
J. Biol. Chem. 280, 36013-36018
   Abstract »    Full Text »    PDF »
The Dual-Specificity Protein Phosphatase DUSP9/MKP-4 Is Essential for Placental Function but Is Not Required for Normal Embryonic Development.
G. R. Christie, D. J. Williams, F. MacIsaac, R. J. Dickinson, I. Rosewell, and S. M. Keyse (2005)
Mol. Cell. Biol. 25, 8323-8333
   Abstract »    Full Text »    PDF »
Phosphorylation of Phosphoprotein Enriched in Astrocytes (PEA-15) Regulates Extracellular Signal-regulated Kinase-dependent Transcription and Cell Proliferation.
J. Krueger, F.-L. Chou, A. Glading, E. Schaefer, and M. H. Ginsberg (2005)
Mol. Biol. Cell 16, 3552-3561
   Abstract »    Full Text »    PDF »
The Pro33 Isoform of Integrin {beta}3 Enhances Outside-in Signaling in Human Platelets by Regulating the Activation of Serine/Threonine Phosphatases.
K. V. Vijayan, Y. Liu, W. Sun, M. Ito, and P. F. Bray (2005)
J. Biol. Chem. 280, 21756-21762
   Abstract »    Full Text »    PDF »
The Noncatalytic Amino Terminus of Mitogen-Activated Protein Kinase Phosphatase 1 Directs Nuclear Targeting and Serum Response Element Transcriptional Regulation.
J. J. Wu, L. Zhang, and A. M. Bennett (2005)
Mol. Cell. Biol. 25, 4792-4803
   Abstract »    Full Text »    PDF »
The Benzo[c]phenanthridine Alkaloid, Sanguinarine, Is a Selective, Cell-active Inhibitor of Mitogen-activated Protein Kinase Phosphatase-1.
A. Vogt, A. Tamewitz, J. Skoko, R. P. Sikorski, K. A. Giuliano, and J. S. Lazo (2005)
J. Biol. Chem. 280, 19078-19086
   Abstract »    Full Text »    PDF »
Protein Phosphatase 2A Activity Associated with Golgi Membranes during the G2/M Phase May Regulate Phosphorylation of ERK2.
C. N. Hancock, S. Dangi, and P. Shapiro (2005)
J. Biol. Chem. 280, 11590-11598
   Abstract »    Full Text »    PDF »
Feedback interactions between MKP3 and ERK MAP kinase control scleraxis expression and the specification of rib progenitors in the developing chick somite.
T. G. Smith, D. Sweetman, M. Patterson, S. M. Keyse, and A. Munsterberg (2005)
Development 132, 1305-1314
   Abstract »    Full Text »    PDF »
Specific Inactivation and Nuclear Anchoring of Extracellular Signal-Regulated Kinase 2 by the Inducible Dual-Specificity Protein Phosphatase DUSP5.
M. Mandl, D. N. Slack, and S. M. Keyse (2005)
Mol. Cell. Biol. 25, 1830-1845
   Abstract »    Full Text »    PDF »
Reversible Oxidation of ERK-directed Protein Phosphatases Drives Oxidative Toxicity in Neurons.
D. J. Levinthal and D. B. DeFranco (2005)
J. Biol. Chem. 280, 5875-5883
   Abstract »    Full Text »    PDF »
Extracellular Signal-Regulated Kinases Phosphorylate Mitogen-Activated Protein Kinase Phosphatase 3/DUSP6 at Serines 159 and 197, Two Sites Critical for Its Proteasomal Degradation.
S. Marchetti, C. Gimond, J.-C. Chambard, T. Touboul, D. Roux, J. Pouyssegur, and G. Pages (2005)
Mol. Cell. Biol. 25, 854-864
   Abstract »    Full Text »    PDF »
Both ERK and Wnt/{beta}-catenin pathways are involved in Wnt3a-induced proliferation.
M.-S. Yun, S.-E. Kim, S. H. Jeon, J.-S. Lee, and K.-Y. Choi (2005)
J. Cell Sci. 118, 313-322
   Abstract »    Full Text »    PDF »
Molecular Determinants of Substrate Recognition in Hematopoietic Protein-tyrosine Phosphatase.
Z. Huang, B. Zhou, and Z.-Y. Zhang (2004)
J. Biol. Chem. 279, 52150-52159
   Abstract »    Full Text »    PDF »
MAP Kinase Phosphatase 3 (MKP3) Interacts with and Is Phosphorylated by Protein Kinase CK2{alpha}.
M. Castelli, M. Camps, C. Gillieron, D. Leroy, S. Arkinstall, C. Rommel, and A. Nichols (2004)
J. Biol. Chem. 279, 44731-44739
   Abstract »    Full Text »    PDF »
Mechanisms Regulating the Constitutive Activation of the Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway in Ovarian Cancer and the Effect of Ribonucleic Acid Interference for ERK1/2 on Cancer Cell Proliferation.
R. Steinmetz, H. A. Wagoner, P. Zeng, J. R. Hammond, T. S. Hannon, J. L. Meyers, and O. H. Pescovitz (2004)
Mol. Endocrinol. 18, 2570-2582
   Abstract »    Full Text »    PDF »
MKP-1 expression and stabilization and cGK I{alpha} prevent diabetes- associated abnormalities in VSMC migration.
A. Jacob, A. Smolenski, S. M. Lohmann, and N. Begum (2004)
Am J Physiol Cell Physiol 287, C1077-C1086
   Abstract »    Full Text »    PDF »
Both Nuclear-Cytoplasmic Shuttling of the Dual Specificity Phosphatase MKP-3 and Its Ability to Anchor MAP Kinase in the Cytoplasm Are Mediated by a Conserved Nuclear Export Signal.
M. Karlsson, J. Mathers, R. J. Dickinson, M. Mandl, and S. M. Keyse (2004)
J. Biol. Chem. 279, 41882-41891
   Abstract »    Full Text »    PDF »
D1 Dopamine Receptor Mediates Dopamine-induced Cytotoxicity via the ERK Signal Cascade.
J. Chen, M. Rusnak, R. R. Luedtke, and A. Sidhu (2004)
J. Biol. Chem. 279, 39317-39330
   Abstract »    Full Text »    PDF »
Ras, PI3-kinase and mTOR signaling in cardiac hypertrophy.
C. G Proud (2004)
Cardiovasc Res 63, 403-413
   Abstract »    Full Text »    PDF »
The Hepatitis E Virus Open Reading Frame 3 Protein Activates ERK through Binding and Inhibition of the MAPK Phosphatase.
A. Kar-Roy, H. Korkaya, R. Oberoi, S. K. Lal, and S. Jameel (2004)
J. Biol. Chem. 279, 28345-28357
   Abstract »    Full Text »    PDF »
A Semidominant Mutation in an Arabidopsis Mitogen-Activated Protein Kinase Phosphatase-Like Gene Compromises Cortical Microtubule Organization.
K. Naoi and T. Hashimoto (2004)
PLANT CELL 16, 1841-1853
   Abstract »    Full Text »    PDF »
A role for MKP3 in axial patterning of the zebrafish embryo.
M. Tsang, S. Maegawa, A. Kiang, R. Habas, E. Weinberg, and I. B. Dawid (2004)
Development 131, 2769-2779
   Abstract »    Full Text »    PDF »
Tumor Cell Responses to a Novel Glutathione S-Transferase-Activated Nitric Oxide-Releasing Prodrug.
V. J. Findlay, D. M. Townsend, J. E. Saavedra, G. S. Buzard, M. L. Citro, L. K. Keefer, X. Ji, and K. D. Tew (2004)
Mol. Pharmacol. 65, 1070-1079
   Abstract »    Full Text »
Promotion and Attenuation of FGF Signaling Through the Ras-MAPK Pathway.
M. Tsang and I. B. Dawid (2004)
Sci. STKE 2004, pe17
   Abstract »    Full Text »    PDF »
Nerve Growth Factor-dependent Survival of CESS B Cell Line Is Mediated by Increased Expression and Decreased Degradation of MAPK Phosphatase 1.
P. Rosini, G. De Chiara, P. Bonini, M. Lucibello, M. E. Marcocci, E. Garaci, F. Cozzolino, and M. Torcia (2004)
J. Biol. Chem. 279, 14016-14023
   Abstract »    Full Text »    PDF »
Reciprocal Regulation between Slt2 MAPK and Isoforms of Msg5 Dual-specificity Protein Phosphatase Modulates the Yeast Cell Integrity Pathway.
M. Flandez, I. C. Cosano, C. Nombela, H. Martin, and M. Molina (2004)
J. Biol. Chem. 279, 11027-11034
   Abstract »    Full Text »    PDF »
Effective Dephosphorylation of Src Substrates by SHP-1.
C. Frank, C. Burkhardt, D. Imhof, J. Ringel, O. Zschornig, K. Wieligmann, M. Zacharias, and F.-D. Bohmer (2004)
J. Biol. Chem. 279, 11375-11383
   Abstract »    Full Text »    PDF »
Regulation of Ras-MAPK pathway mitogenic activity by restricting nuclear entry of activated MAPK in endoderm differentiation of embryonic carcinoma and stem cells.
E. R. Smith, J. L. Smedberg, M. E. Rula, and X.-X. Xu (2004)
J. Cell Biol. 164, 689-699
   Abstract »    Full Text »    PDF »
MKP-3 Has Essential Roles as a Negative Regulator of the Ras/Mitogen-Activated Protein Kinase Pathway during Drosophila Development.
M. Kim, G.-H. Cha, S. Kim, J. H. Lee, J. Park, H. Koh, K.-Y. Choi, and J. Chung (2004)
Mol. Cell. Biol. 24, 573-583
   Abstract »    Full Text »    PDF »
Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons.
C. Crosio, E. Heitz, C. D. Allis, E. Borrelli, and P. Sassone-Corsi (2003)
J. Cell Sci. 116, 4905-4914
   Abstract »    Full Text »    PDF »
IBR5, a Dual-Specificity Phosphatase-Like Protein Modulating Auxin and Abscisic Acid Responsiveness in Arabidopsis.
M. Monroe-Augustus, B. K. Zolman, and B. Bartel (2003)
PLANT CELL 15, 2979-2991
   Abstract »    Full Text »    PDF »
The Antidiabetic Agent Sodium Tungstate Activates Glycogen Synthesis through an Insulin Receptor-independent Pathway.
J. E. Dominguez, M.a C. Munoz, D. Zafra, I. Sanchez-Perez, S. Baque, M. Caron, C. Mercurio, A. Barbera, R. Perona, R. Gomis, et al. (2003)
J. Biol. Chem. 278, 42785-42794
   Abstract »    Full Text »    PDF »
Constitutive Induction of p-Erk1/2 Accompanied by Reduced Activities of Protein Phosphatases 1 and 2A and MKP3 Due to Reactive Oxygen Species during Cellular Senescence.
H. S. Kim, M.-C. Song, I. H. Kwak, T. J. Park, and I. K. Lim (2003)
J. Biol. Chem. 278, 37497-37510
   Abstract »    Full Text »    PDF »
A Bipartite Mechanism for ERK2 Recognition by Its Cognate Regulators and Substrates.
J. Zhang, B. Zhou, C.-F. Zheng, and Z.-Y. Zhang (2003)
J. Biol. Chem. 278, 29901-29912
   Abstract »    Full Text »    PDF »
The Drosophila dual-specificity ERK phosphatase DMKP3 cooperates with the ERK tyrosine phosphatase PTP-ER.
F. Rintelen, E. Hafen, and K. Nairz (2003)
Development 130, 3479-3490
   Abstract »    Full Text »    PDF »
ERK1/2 Achieves Sustained Activation by Stimulating MAPK Phosphatase-1 Degradation via the Ubiquitin-Proteasome Pathway.
Y.-W. Lin, S.-M. Chuang, and J.-L. Yang (2003)
J. Biol. Chem. 278, 21534-21541
   Abstract »    Full Text »    PDF »
Inactivation of Dual-Specificity Phosphatases Is Involved in the Regulation of Extracellular Signal-Regulated Kinases by Heat Shock and Hsp72.
J. Yaglom, C. O'Callaghan-Sunol, V. Gabai, and M. Y. Sherman (2003)
Mol. Cell. Biol. 23, 3813-3824
   Abstract »    Full Text »    PDF »
Mapping of Synergistic Components of Weakly Interacting Protein-Protein Motifs Using Arrays of Paired Peptides.
X. Espanel, S. Walchli, T. Ruckle, A. Harrenga, M. Huguenin-Reggiani, and R. Hooft van Huijsduijnen (2003)
J. Biol. Chem. 278, 15162-15167
   Abstract »    Full Text »    PDF »
Regulation of the Interleukin-1-induced Signaling Pathways by a Novel Member of the Protein Phosphatase 2C Family (PP2Cepsilon ).
M. G. Li, K. Katsura, H. Nomiyama, K.-i. Komaki, J. Ninomiya-Tsuji, K. Matsumoto, T. Kobayashi, and S. Tamura (2003)
J. Biol. Chem. 278, 12013-12021
   Abstract »    Full Text »    PDF »
Modulation of Cellular Signaling Pathways: Prospects for Targeted Therapy in Hematological Malignancies.
F. Ravandi, M. Talpaz, and Z. Estrov (2003)
Clin. Cancer Res. 9, 535-550
   Abstract »    Full Text »    PDF »
Dexamethasone Causes Sustained Expression of Mitogen-Activated Protein Kinase (MAPK) Phosphatase 1 and Phosphatase-Mediated Inhibition of MAPK p38.
M. Lasa, S. M. Abraham, C. Boucheron, J. Saklatvala, and A. R. Clark (2002)
Mol. Cell. Biol. 22, 7802-7811
   Abstract »    Full Text »    PDF »
Responding to Hypoxia: Lessons From a Model Cell Line.
K. A. Seta, Z. Spicer, Y. Yuan, G. Lu, and D. E. Millhorn (2002)
Sci. STKE 2002, re11
   Abstract »    Full Text »    PDF »
Phosphotyrosine-specific Phosphatase PTP-SL Regulates the ERK5 Signaling Pathway.
M. Buschbeck, J. Eickhoff, M. N. Sommer, and A. Ullrich (2002)
J. Biol. Chem. 277, 29503-29509
   Abstract »    Full Text »    PDF »
A Novel Dual Specificity Phosphatase SKRP1 Interacts with the MAPK Kinase MKK7 and Inactivates the JNK MAPK Pathway. IMPLICATION FOR THE PRECISE REGULATION OF THE PARTICULAR MAPK PATHWAY.
T. Zama, R. Aoki, T. Kamimoto, K. Inoue, Y. Ikeda, and M. Hagiwara (2002)
J. Biol. Chem. 277, 23909-23918
   Abstract »    Full Text »    PDF »
Cell adhesion differentially regulates the nucleocytoplasmic distribution of active MAP kinases.
A. E. Aplin, B. P. Hogan, J. Tomeu, and R. L. Juliano (2002)
J. Cell Sci. 115, 2781-2790
   Abstract »    Full Text »    PDF »
Shear Stress-Induced Endothelial Cell Migration Involves Integrin Signaling Via the Fibronectin Receptor Subunits {alpha}5 and {beta}1.
C. Urbich, E. Dernbach, A. Reissner, M. Vasa, A. M. Zeiher, and S. Dimmeler (2002)
Arterioscler Thromb Vasc Biol 22, 69-75
   Abstract »    Full Text »    PDF »
An Early Growth Response Protein (Egr) 1 cis-Element Is Required for Gonadotropin-releasing Hormone-induced Mitogen-activated Protein Kinase Phosphatase 2 Gene Expression.
T. Zhang, M. W. Wolfe, and M. S. Roberson (2001)
J. Biol. Chem. 276, 45604-45613
   Abstract »    Full Text »    PDF »
Constitutive Activation of Extracellular Signal-regulated Kinase 2 by Synergistic Point Mutations.
M. A. Emrick, A. N. Hoofnagle, A. S. Miller, L. F. T. Eyck, and N. G. Ahn (2001)
J. Biol. Chem. 276, 46469-46479
   Abstract »    Full Text »    PDF »
Hematopoietic Protein Tyrosine Phosphatase Suppresses Extracellular Stimulus-Regulated Kinase Activation.
M. Gronda, S. Arab, B. Iafrate, H. Suzuki, and B. W. Zanke (2001)
Mol. Cell. Biol. 21, 6851-6858
   Abstract »    Full Text »    PDF »
A Novel Mitogen-Activated Protein Kinase Phosphatase Is an Important Negative Regulator of Lipopolysaccharide-Mediated c-Jun N-Terminal Kinase Activation in Mouse Macrophage Cell Lines.
T. Matsuguchi, T. Musikacharoen, T. R. Johnson, A. S. Kraft, and Y. Yoshikai (2001)
Mol. Cell. Biol. 21, 6999-7009
   Abstract »    Full Text »    PDF »
Activation of Salicylic Acid-Induced Protein Kinase, a Mitogen-Activated Protein Kinase, Induces Multiple Defense Responses in Tobacco.
S. Zhang and Y. Liu (2001)
PLANT CELL 13, 1877-1889
   Abstract »    Full Text »    PDF »
Tyrosine-Phosphorylated Extracellular Signal-Regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure.
H. Cha and P. Shapiro (2001)
J. Cell Biol. 153, 1355-1368
   Abstract »    Full Text »    PDF »
Integrin-Mediated Adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1.
A. E. Aplin, S. A. Stewart, R. K. Assoian, and R.L. Juliano (2001)
J. Cell Biol. 153, 273-282
   Abstract »    Full Text »    PDF »
Sustained Signaling by Phospholipase C-{gamma} Mediates Nerve Growth Factor-Triggered Gene Expression.
D.-Y. Choi, J. J. Toledo-Aral, R. Segal, and S. Halegoua (2001)
Mol. Cell. Biol. 21, 2695-2705
   Abstract »    Full Text »    PDF »
The Serine/Threonine Phosphatase, PP2A: Endogenous Regulator of Inflammatory Cell Signaling.
T. P. Shanley, N. Vasi, A. Denenberg, and H. R. Wong (2001)
J. Immunol. 166, 966-972
   Abstract »    Full Text »    PDF »
Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity.
K Halfar, C Rommel, H Stocker, and E Hafen (2001)
Development 128, 1687-1696
   Abstract »    PDF »
Negative-Feedback Regulation of CD28 Costimulation by a Novel Mitogen-Activated Protein Kinase Phosphatase, MKP6.
F. Marti, A. Krause, N. H. Post, C. Lyddane, B. Dupont, M. Sadelain, and P. D. King (2001)
J. Immunol. 166, 197-206
   Abstract »    Full Text »    PDF »
Antiinflammatory Effects of Estrogen on Microglial Activation.
A. J. Bruce-Keller, J. L. Keeling, J. N. Keller, F. F. Huang, S. Camondola, and M. P. Mattson (2000)
Endocrinology 141, 3646-3656
   Abstract »    Full Text »    PDF »
MAPK signaling and the kidney.
W. Tian, Z. Zhang, and D. M. Cohen (2000)
Am J Physiol Renal Physiol 279, F593-F604
   Abstract »    Full Text »    PDF »
Activation of JNK, p38 and ERK mitogen-activated protein kinases by chromium(VI) is mediated through oxidative stress but does not affect cytotoxicity.
S.-M. Chuang, G.-Y. Liou, and J.-L. Yang (2000)
Carcinogenesis 21, 1491-1500
   Abstract »    Full Text »    PDF »
A Role for the MEK-MAPK Pathway in Okadaic Acid-Induced Meiotic Resumption of Incompetent Growing Mouse Oocytes.
C. de Vantéry Arrighi, A. Campana, and S. Schorderet-Slatkine (2000)
Biol Reprod 63, 658-665
   Abstract »    Full Text »
Roles of JNK, p38 and ERK mitogen-activated protein kinases in the growth inhibition and apoptosis induced by cadmium.
S.-M. Chuang, I-C. Wang, and J.-L. Yang (2000)
Carcinogenesis 21, 1423-1432
   Abstract »    Full Text »    PDF »
Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways.
C. Ruwhof and A. van der Laarse (2000)
Cardiovasc Res 47, 23-37
   Abstract »    Full Text »    PDF »
Abrogation of Nerve Growth Factor-induced Terminal Differentiation by ret Oncogene Involves Perturbation of Nuclear Translocation of ERK.
G. L. Colucci-D'Amato, A. D'Alessio, D. Califano, G. Cali, C. Rizzo, L. Nitsch, G. Santelli, and V. de Franciscis (2000)
J. Biol. Chem. 275, 19306-19314
   Abstract »    Full Text »    PDF »
The Dual-Specificity Protein Phosphatase Yvh1p Regulates Sporulation, Growth, and Glycogen Accumulation Independently of Catalytic Activity in Saccharomyces cerevisiae via the Cyclic AMP-Dependent Protein Kinase Cascade.
A. E. Beeser and T. G. Cooper (2000)
J. Bacteriol. 182, 3517-3528
   Abstract »    Full Text »    PDF »
Mechanistic Basis for Catalytic Activation of Mitogen-activated Protein Kinase Phosphatase 3 by Extracellular Signal-regulated Kinase.
C. C. Fjeld, A. E. Rice, Y. Kim, K. R. Gee, and J. M. Denu (2000)
J. Biol. Chem. 275, 6749-6757
   Abstract »    Full Text »    PDF »
Posttranslational Modification of Bcl-2 Facilitates Its Proteasome-Dependent Degradation: Molecular Characterization of the Involved Signaling Pathway.
K. Breitschopf, J. Haendeler, P. Malchow, A. M. Zeiher, and S. Dimmeler (2000)
Mol. Cell. Biol. 20, 1886-1896
   Abstract »    Full Text »    PDF »
Dual specificity phosphatases: a gene family for control of MAP kinase function.
M. CAMPS, A. NICHOLS, and S. ARKINSTALL (2000)
FASEB J 14, 6-16
   Abstract »    Full Text »
Mechanism of Mitogen-activated Protein Kinase Phosphatase-3 Activation by ERK2.
B. Zhou and Z.-Y. Zhang (1999)
J. Biol. Chem. 274, 35526-35534
   Abstract »    Full Text »    PDF »
A specific protein-protein interaction accounts for the in vivo substrate selectivity of Ptp3 towards the Fus3 MAP kinase.
X.-L. Zhan and K.-L. Guan (1999)
Genes & Dev. 13, 2811-2827
   Abstract »    Full Text »
Activation of the Saccharomyces cerevisiae Filamentation/Invasion Pathway by Osmotic Stress in High-Osmolarity Glycogen Pathway Mutants.
K. D. Davenport, K. E. Williams, B. D. Ullmann, and M. C. Gustin (1999)
Genetics 153, 1091-1103
   Abstract »    Full Text »
Identification of a Cytoplasmic-Retention Sequence in ERK2.
H. Rubinfeld, T. Hanoch, and R. Seger (1999)
J. Biol. Chem. 274, 30349-30352
   Abstract »    Full Text »    PDF »


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