Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 3 October 1997:
Vol. 278. no. 5335, pp. 103 - 106
DOI: 10.1126/science.278.5335.103
Prev | Table of Contents | Next

Reports

Ste5 RING-H2 Domain: Role in Ste4-Promoted Oligomerization for Yeast Pheromone Signaling

Carla Inouye, * Namrita Dhillon, *dagger Jeremy Thorner ddagger

Ste5 is a scaffold for the mitogen-activated protein kinase (MAPK) cascade components in a yeast pheromone response pathway. Ste5 also associates with Ste4, the beta  subunit of a heterotrimeric guanine nucleotide-binding protein, potentially linking receptor activation to stimulation of the MAPK cascade. A RING-H2 motif at the Ste5 amino terminus is apparently essential for function because Ste5(C177S) and Ste5(C177A C180A) mutants did not rescue the mating defect of a ste5Delta cell. In vitro Ste5(C177A C180A) bound each component of the MAPK cascade, but not Ste4. Unlike wild-type Ste5, the mutant did not appear to oligomerize; however, when fused to a heterologous dimerization domain (glutathione S-transferase), the chimeric protein restored mating in an ste5Delta cell and an ste4Delta ste5Delta double mutant. Thus, the RING-H2 domain mediates Ste4-Ste5 interaction, which is a prerequisite for Ste5-Ste5 self-association and signaling.

Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720-3202, USA.
*   These authors contributed equally to this paper.

dagger    Present address: Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, Bethesda, MD 20892-5431, USA.

ddagger    To whom correspondence should be addressed. E-mail: jthorner{at}mendel.berkeley.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Nucleus-Specific and Cell Cycle-Regulated Degradation of Mitogen-Activated Protein Kinase Scaffold Protein Ste5 Contributes to the Control of Signaling Competence.
L. S. Garrenton, A. Braunwarth, S. Irniger, E. Hurt, M. Kunzler, and J. Thorner (2009)
Mol. Cell. Biol. 29, 582-601
   Abstract »    Full Text »    PDF »
Oligomerization Regulates the Localization of Cdc24, the Cdc42 Activator in Saccharomyces cerevisiae.
C. Mionnet, S. Bogliolo, and R. A. Arkowitz (2008)
J. Biol. Chem. 283, 17515-17530
   Abstract »    Full Text »    PDF »
Counteractive Control of Polarized Morphogenesis during Mating by Mitogen-activated Protein Kinase Fus3 and G1 Cyclin-dependent Kinase.
L. Yu, M. Qi, M. A. Sheff, and E. A. Elion (2008)
Mol. Biol. Cell 19, 1739-1752
   Abstract »    Full Text »    PDF »
Distinct Roles for Two G{alpha} G Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein.
S. C. Strickfaden and P. M. Pryciak (2008)
Mol. Biol. Cell 19, 181-197
   Abstract »    Full Text »    PDF »
Mapping dynamic protein interactions in MAP kinase signaling using live-cell fluorescence fluctuation spectroscopy and imaging.
B. D. Slaughter, J. W. Schwartz, and R. Li (2007)
PNAS 104, 20320-20325
   Abstract »    Full Text »    PDF »
Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain.
L. S. Garrenton, S. L. Young, and J. Thorner (2006)
Genes & Dev. 20, 1946-1958
   Abstract »    Full Text »    PDF »
Adaptor protein Ste50p links the Ste11p MEKK to the HOG pathway through plasma membrane association..
C. Wu, G. Jansen, J. Zhang, D. Y. Thomas, and M. Whiteway (2006)
Genes & Dev. 20, 734-746
   Abstract »    Full Text »    PDF »
The RA Domain of Ste50 Adaptor Protein Is Required for Delivery of Ste11 to the Plasma Membrane in the Filamentous Growth Signaling Pathway of the Yeast Saccharomyces cerevisiae.
D. M. Truckses, J. E. Bloomekatz, and J. Thorner (2006)
Mol. Cell. Biol. 26, 912-928
   Abstract »    Full Text »    PDF »
Forcing interactions as a genetic screen to identify proteins that exert a defined activity.
M. DeVit, P. J. Cullen, M. Branson, G. F. Sprague Jr., and S. Fields (2005)
Genome Res. 15, 560-565
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinases with Distinct Requirements for Ste5 Scaffolding Influence Signaling Specificity in Saccharomyces cerevisiae.
L. J. Flatauer, S. F. Zadeh, and L. Bardwell (2005)
Mol. Cell. Biol. 25, 1793-1803
   Abstract »    Full Text »    PDF »
Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway.
A. Gruhler, J. V. Olsen, S. Mohammed, P. Mortensen, N. J. Faergeman, M. Mann, and O. N. Jensen (2005)
Mol. Cell. Proteomics 4, 310-327
   Abstract »    Full Text »    PDF »
Localized Feedback Phosphorylation of Ste5p Scaffold by Associated MAPK Cascade.
A. Flotho, D. M. Simpson, M. Qi, and E. A. Elion (2004)
J. Biol. Chem. 279, 47391-47401
   Abstract »    Full Text »    PDF »
Homo-oligomerization Is the Essential Function of the Tandem BRCT Domains in the Checkpoint Protein Crb2.
L.-L. Du, B. A. Moser, and P. Russell (2004)
J. Biol. Chem. 279, 38409-38414
   Abstract »    Full Text »    PDF »
Adapter Protein SH2-B{beta} Undergoes Nucleocytoplasmic Shuttling: Implications for Nerve Growth Factor Induction of Neuronal Differentiation.
L. Chen and C. Carter-Su (2004)
Mol. Cell. Biol. 24, 3633-3647
   Abstract »    Full Text »    PDF »
Membrane Localization, Oligomerization, and Phosphorylation Are Required for Optimal Raf Activation.
C. A. Goetz, J. J. O'Neil, and M. A. Farrar (2003)
J. Biol. Chem. 278, 51184-51189
   Abstract »    Full Text »    PDF »
Regulation of Ste7 Ubiquitination by Ste11 Phosphorylation and the Skp1-Cullin-F-box Complex.
Y. Wang, Q. Ge, D. Houston, J. Thorner, B. Errede, and H. G. Dohlman (2003)
J. Biol. Chem. 278, 22284-22289
   Abstract »    Full Text »    PDF »
Nuclear Export and Plasma Membrane Recruitment of the Ste5 Scaffold Are Coordinated with Oligomerization and Association with Signal Transduction Components.
Y. Wang and E. A. Elion (2003)
Mol. Biol. Cell 14, 2543-2558
   Abstract »    Full Text »    PDF »
Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling.
K. Matsuno, M. Ito, K. Hori, F. Miyashita, S. Suzuki, N. Kishi, S. Artavanis-Tsakonas, and H. Okano (2003)
Development 129, 1049-1059
   Abstract »    Full Text »    PDF »
The Ste5p scaffold.
E. A. Elion (2002)
J. Cell Sci. 114, 3967-3978
   Abstract »    Full Text »    PDF »
Yeast PalA/AIP1/Alix Homolog Rim20p Associates with a PEST-Like Region and Is Required for Its Proteolytic Cleavage.
W. Xu and A. P. Mitchell (2001)
J. Bacteriol. 183, 6917-6923
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions.
G. Pearson, F. Robinson, T. Beers Gibson, B.-e Xu, M. Karandikar, K. Berman, and M. H. Cobb (2001)
Endocr. Rev. 22, 153-183
   Abstract »    Full Text »
Mutations in the YRB1 Gene Encoding Yeast Ran-Binding-Protein-1 That Impair Nucleocytoplasmic Transport and Suppress Yeast Mating Defects.
M. Künzler, J. Trueheart, C. Sette, E. Hurt, and J. Thorner (2001)
Genetics 157, 1089-1105
   Abstract »    Full Text »
Mutational Analysis Suggests That Activation of the Yeast Pheromone Response Mitogen-activated Protein Kinase Pathway Involves Conformational Changes in the Ste5 Scaffold Protein.
C. Sette, C. J. Inouye, S. L. Stroschein, P. J. Iaquinta, and J. Thorner (2000)
Mol. Biol. Cell 11, 4033-4049
   Abstract »    Full Text »
What Do Scaffold Proteins Really Do?.
J. E. Ferrell Jr. (2000)
Sci. STKE 2000, pe1
   Abstract »    Full Text »    PDF »
Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3.
N. Kelkar, S. Gupta, M. Dickens, and R. J. Davis (2000)
Mol. Cell. Biol. 20, 1030-1043
   Abstract »    Full Text »
Feedback Phosphorylation of the Yeast a-Factor Receptor Requires Activation of the Downstream Signaling Pathway from G Protein through Mitogen-Activated Protein Kinase.
Y. Feng and N. G. Davis (2000)
Mol. Cell. Biol. 20, 563-574
   Abstract »    Full Text »
Stabilization of the MDM2 Oncoprotein by Interaction with the Structurally Related MDMX Protein.
D. A. Sharp, S. A. Kratowicz, M. J. Sank, and D. L. George (1999)
J. Biol. Chem. 274, 38189-38196
   Abstract »    Full Text »    PDF »
Leucine Zipper-mediated Homodimerization of the Adaptor Protein c-Cbl. A ROLE IN c-Cbl's TYROSINE PHOSPHORYLATION AND ITS ASSOCIATION WITH EPIDERMAL GROWTH FACTOR RECEPTOR.
M. Bartkiewicz, A. Houghton, and R. Baron (1999)
J. Biol. Chem. 274, 30887-30895
   Abstract »    Full Text »    PDF »
The JIP Group of Mitogen-Activated Protein Kinase Scaffold Proteins.
J. Yasuda, A. J. Whitmarsh, J. Cavanagh, M. Sharma, and R. J. Davis (1999)
Mol. Cell. Biol. 19, 7245-7254
   Abstract »    Full Text »    PDF »
The RING Finger Motif of Photomorphogenic Repressor COP1 Specifically Interacts with the RING-H2 Motif of a Novel Arabidopsis Protein.
K. U. Torii, C. D. Stoop-Myer, H. Okamoto, J. E. Coleman, M. Matsui, and X. W. Deng (1999)
J. Biol. Chem. 274, 27674-27681
   Abstract »    Full Text »    PDF »
Characterization of Fus3 Localization: Active Fus3 Localizes in Complexes of Varying Size and Specific Activity.
K.-Y. Choi, J. E. Kranz, S. K. Mahanty, K.-S. Park, and E. A. Elion (1999)
Mol. Biol. Cell 10, 1553-1568
   Abstract »    Full Text »
SAG, a Novel Zinc RING Finger Protein That Protects Cells from Apoptosis Induced by Redox Agents.
H. Duan, Y. Wang, M. Aviram, M. Swaroop, J. A. Loo, J. Bian, Y. Tian, T. Mueller, C. L. Bisgaier, and Y. Sun (1999)
Mol. Cell. Biol. 19, 3145-3155
   Abstract »    Full Text »    PDF »
KSR-1 Binds to G-protein beta gamma Subunits and Inhibits beta gamma -induced Mitogen-activated Protein Kinase Activation.
B. Bell, H. Xing, K. Yan, N. Gautam, and A. J. Muslin (1999)
J. Biol. Chem. 274, 7982-7986
   Abstract »    Full Text »    PDF »
POG1, a Novel Yeast Gene, Promotes Recovery From Pheromone Arrest via the G1 Cyclin CLN2.
M. A. Leza and E. A. Elion (1999)
Genetics 151, 531-543
   Abstract »    Full Text »
Receptor Inhibition of Pheromone Signaling Is Mediated by the Ste4p Gbeta Subunit.
J. Kim, A. Couve, and J. P. Hirsch (1999)
Mol. Cell. Biol. 19, 441-449
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human.
C. WIDMANN, S. GIBSON, M. B. JARPE, and G. L. JOHNSON (1999)
Physiol Rev 79, 143-180
   Abstract »    Full Text »    PDF »
MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae.
M. C. Gustin, J. Albertyn, M. Alexander, and K. Davenport (1998)
Microbiol. Mol. Biol. Rev. 62, 1264-1300
   Abstract »    Full Text »    PDF »
Mapping of a Yeast G Protein ß{gamma} Signaling Interaction.
S. J. Dowell, A. L. Bishop, S. L. Dyos, A. J. Brown, and M. S. Whiteway (1998)
Genetics 150, 1407-1417
   Abstract »    Full Text »
The Role of Far1p in Linking the Heterotrimeric G Protein to Polarity Establishment Proteins During Yeast Mating.
A. Butty, P. M. Pryciak, L. S. Huang, I. Herskowitz, and M. Peter (1998)
Science 282, 1511-1516
   Abstract »    Full Text »
The Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding.
D. E. Klein, A. Lee, D. W. Frank, M. S. Marks, and M. A. Lemmon (1998)
J. Biol. Chem. 273, 27725-27733
   Abstract »    Full Text »    PDF »
Localization of Splenic B Cells Activated for Switch Recombination by In Situ Hybridization with I{gamma}1 Switch Transcript and Rad51 Probes.
M.-C. Peakman and N. Maizels (1998)
J. Immunol. 161, 4008-4015
   Abstract »    Full Text »    PDF »
Tumor necrosis factor receptor-associated factors (TRAFs)---a family of adapter proteins that regulates life and death.
R. H. Arch, R. W. Gedrich, and C. B. Thompson (1998)
Genes & Dev. 12, 2821-2830
   Full Text »
The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae.
S. M. O'Rourke and I. Herskowitz (1998)
Genes & Dev. 12, 2874-2886
   Abstract »    Full Text »
Membrane recruitment of the kinase cascade scaffold protein Ste5 by the Gbeta gamma complex underlies activation of the yeast pheromone response pathway.
P. M. Pryciak and F. A. Huntress (1998)
Genes & Dev. 12, 2684-2697
   Abstract »    Full Text »
Reactive Oxygen Species- and Dimerization-induced Activation of Apoptosis Signal-regulating Kinase 1 in Tumor Necrosis Factor-alpha Signal Transduction.
Y. Gotoh and J. A. Cooper (1998)
J. Biol. Chem. 273, 17477-17482
   Abstract »    Full Text »    PDF »
Pheromone-Dependent G1 Cell Cycle Arrest Requires Far1 Phosphorylation, but May Not Involve Inhibition of Cdc28-Cln2 Kinase, In Vivo.
A. Gartner, D.-I. Jeoung, S. Bourlat, F. R. Cross, and G. Ammerer (1998)
Mol. Cell. Biol. 18, 3681-3691
   Abstract »    Full Text »
14-3-3 Proteins Interact with Specific MEK Kinases.
G. R. Fanger, C. Widmann, A. C. Porter, S. Sather, G. L. Johnson, and R. R. Vaillancourt (1998)
J. Biol. Chem. 273, 3476-3483
   Abstract »    Full Text »    PDF »
The Many Faces of G Protein Signaling.
H. E. Hamm (1998)
J. Biol. Chem. 273, 669-672
   Full Text »    PDF »
Membrane Localization of Raf Assists Engagement of Downstream Effectors.
M. A. Farrar, J. Tian, and R. M. Perlmutter (2000)
J. Biol. Chem. 275, 31318-31324
   Abstract »    Full Text »    PDF »
A Conserved Docking Site in MEKs Mediates High-affinity Binding to MAP Kinases and Cooperates with a Scaffold Protein to Enhance Signal Transmission.
A. J. Bardwell, L. J. Flatauer, K. Matsukuma, J. Thorner, and L. Bardwell (2001)
J. Biol. Chem. 276, 10374-10386
   Abstract »    Full Text »    PDF »
Identification of Novel Pheromone-response Regulators through Systematic Overexpression of 120 Protein Kinases in Yeast.
S. A. Burchett, A. Scott, B. Errede, and H. G. Dohlman (2001)
J. Biol. Chem. 276, 26472-26478
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)