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Science 22 November 1996:
Vol. 274. no. 5291, pp. 1374 - 1376
DOI: 10.1126/science.274.5291.1374
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Reports

RAC Regulation of Actin Polymerization and Proliferation by a Pathway Distinct from Jun Kinase

Tom Joneson, * Michele McDonough, * Dafna Bar-Sagi, Linda Van Aelst dagger

The RAC guanine nucleotide binding proteins regulate multiple biological activities, including actin polymerization, activation of the Jun kinase (JNK) cascade, and cell proliferation. RAC effector loop mutants were identified that separate the ability of RAC to interact with different downstream effectors. One mutant of activated human RAC protein, RACV12H40 (with valine and histidine substituted at position 12 and 40, respectively), was defective in binding to PAK3, a Ste20-related p21-activated kinase (PAK), but bound to POR1, a RAC-binding protein. This mutant failed to stimulate PAK and JNK activity but still induced membrane ruffling and mediated transformation. A second mutant, RACV12L37 (with leucine substituted at position 37), which bound PAK but not POR1, induced JNK activation but was defective in inducing membrane ruffling and transformation. These results indicate that the effects of RAC on the JNK cascade and on actin polymerization and cell proliferation are mediated by distinct effector pathways that diverge at the level of RAC itself.

T. Joneson and D. Bar-Sagi, Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, NY 11794, USA.
M. McDonough and L. Van Aelst, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed.

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Regulation of Actin Polymerization in Cell-free Systems by GTP{gamma}S and Cdc42.
S. H. Zigmond, M. Joyce, J. Borleis, G. M. Bokoch, and P. N. Devreotes (1997)
J. Cell Biol. 138, 363-374
   Abstract »    Full Text »    PDF »
IQGAP1, a Rac- and Cdc42-binding Protein, Directly Binds and Cross-links Microfilaments.
A.-M. Bashour, A. T. Fullerton, M. J. Hart, and G. S. Bloom (1997)
J. Cell Biol. 137, 1555-1566
   Abstract »    Full Text »    PDF »
Kalirin, a Cytosolic Protein with Spectrin-like and GDP/GTP Exchange Factor-like Domains That Interacts with Peptidylglycine alpha -Amidating Monooxygenase, an Integral Membrane Peptide-processing Enzyme.
M. R. Alam, R. C. Johnson, D. N. Darlington, T. A. Hand, R. E. Mains, and B. A. Eipper (1997)
J. Biol. Chem. 272, 12667-12675
   Abstract »    Full Text »    PDF »
Arfaptin 1,a Putative Cytosolic Target Protein of ADP-ribosylation Factor, Is Recruited to Golgi Membranes.
H. Kanoh, B.-T. Williger, and J. H. Exton (1997)
J. Biol. Chem. 272, 5421-5429
   Abstract »    Full Text »    PDF »
p21-activated Kinase Links Rac/Cdc42 Signaling to Merlin.
G.-H. Xiao, A. Beeser, J. Chernoff, and J. R. Testa (2002)
J. Biol. Chem. 277, 883-886
   Abstract »    Full Text »    PDF »
Cdc42Hs and Rac1 GTPases Induce the Collapse of the Vimentin Intermediate Filament Network.
M. Meriane, S. Mary, F. Comunale, E. Vignal, P. Fort, and C. Gauthier-Rouviere (2000)
J. Biol. Chem. 275, 33046-33052
   Abstract »    Full Text »    PDF »
An Oncogenic Epidermal Growth Factor Receptor Signals via a p21-activated Kinase-Caldesmon-Myosin Phosphotyrosine Complex.
M. J. McManus, J. L. Boerner, A. J. Danielsen, Z. Wang, F. Matsumura, and N. J. Maihle (2000)
J. Biol. Chem. 275, 35328-35334
   Abstract »    Full Text »    PDF »
Implication of a Small GTPase Rac1 in the Activation of c-Jun N-terminal Kinase and Heat Shock Factor in Response to Heat Shock.
S. I. Han, S. Y. Oh, S. H. Woo, K. H. Kim, J.-H. Kim, H. D. Kim, and H. S. Kang (2001)
J. Biol. Chem. 276, 1889-1895
   Abstract »    Full Text »    PDF »
Differential Activation of the Rac Pathway by Ha-Ras and K-Ras.
A. B. Walsh and D. Bar-Sagi (2001)
J. Biol. Chem. 276, 15609-15615
   Abstract »    Full Text »    PDF »


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