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Science 23 January 1998:
Vol. 279. no. 5350, pp. 560 - 563
DOI: 10.1126/science.279.5350.560
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Reports

Coupling of Ras and Rac Guanosine Triphosphatases Through the Ras Exchanger Sos

Anjaruwee S. Nimnual, Bogdan A. Yatsula, Dafna Bar-Sagi *

The Son of Sevenless (Sos) proteins control receptor-mediated activation of Ras by catalyzing the exchange of guanosine diphosphate for guanosine triphosphate on Ras. The NH2-terminal region of Sos contains a Dbl homology (DH) domain in tandem with a pleckstrin homology (PH) domain. In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. The tandem DH-PH domain of Sos (DH-PH-Sos) was defective in Rac activation but regained Rac stimulating activity when it was coexpressed with activated Ras. Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. These results reveal a potential mechanism for coupling of Ras and Rac signaling pathways.

Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
*   To whom correspondence should be addressed: E-mail: barsagi{at}asterix.bio.sunysb.edu

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ZAP-70 Is Essential for the T Cell Antigen Receptor-induced Plasma Membrane Targeting of SOS and Vav in T Cells.
K. V. Salojin, J. Zhang, C. Meagher, and T. L. Delovitch (2000)
J. Biol. Chem. 275, 5966-5975
   Abstract »    Full Text »    PDF »
A Novel Positive Feedback Loop Mediated by the Docking Protein Gab1 and Phosphatidylinositol 3-Kinase in Epidermal Growth Factor Receptor Signaling.
G. A. Rodrigues, M. Falasca, Z. Zhang, S. H. Ong, and J. Schlessinger (2000)
Mol. Cell. Biol. 20, 1448-1459
   Abstract »    Full Text »
A Genetic Screen for Novel Components of the Ras/Mitogen-Activated Protein Kinase Signaling Pathway That Interact With the yan Gene of Drosophila Identifies split ends, a New RNA Recognition Motif-Containing Protein.
I. Rebay, F. Chen, F. Hsiao, P. A. Kolodziej, B. H. Kuang, T. Laverty, C. Suh, M. Voas, A. Williams, and G. M. Rubin (2000)
Genetics 154, 695-712
   Abstract »    Full Text »
Autocrine Signaling through Ras Prevents Apoptosis in Vascular Smooth Muscle Cells in Vitro.
T. Miyamoto and J. C. Fox (2000)
J. Biol. Chem. 275, 2825-2830
   Abstract »    Full Text »    PDF »
p21-Activated Kinase 1 Phosphorylates the Death Agonist Bad and Protects Cells from Apoptosis.
A. Schürmann, A. F. Mooney, L. C. Sanders, M. A. Sells, H. G. Wang, J. C. Reed, and G. M. Bokoch (2000)
Mol. Cell. Biol. 20, 453-461
   Abstract »    Full Text »
Calmodulin and son of sevenless dependent signaling pathways regulate midline crossing of axons in the Drosophila CNS.
J. Fritz and M. VanBerkum (2000)
Development 127, 1991-2000
   Abstract »    PDF »
Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway.
J.-P. Mira, V. Benard, J. Groffen, L. C. Sanders, and U. G. Knaus (2000)
PNAS 97, 185-189
   Abstract »    Full Text »    PDF »
Vinexin Forms a Signaling Complex with Sos and Modulates Epidermal Growth Factor-induced c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activities.
M. Akamatsu, S.-i. Aota, A. Suwa, K. Ueda, T. Amachi, K. M. Yamada, S. K. Akiyama, and N. Kioka (1999)
J. Biol. Chem. 274, 35933-35937
   Abstract »    Full Text »    PDF »
High Affinity IgG Receptor Activation of Src Family Kinases Is Required for Modulation of the Shc-Grb2-Sos Complex and the Downstream Activation of the Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase.
R.-K. Park, A. Erdreich-Epstein, M. Liu, K. D. Izadi, and D. L. Durden (1999)
J. Immunol. 163, 6023-6034
   Abstract »    Full Text »    PDF »
Identification and Characterization of hPEM-2, a Guanine Nucleotide Exchange Factor Specific for Cdc42.
T. Reid, A. Bathoorn, M. R. Ahmadian, and J. G. Collard (1999)
J. Biol. Chem. 274, 33587-33593
   Abstract »    Full Text »    PDF »
An Unexpected Link between the Secretory Path and the Organization of the Nucleus.
J. Nanduri, S. Mitra, C. Andrei, Y. Liu, Y. Yu, M. Hitomi, and A. M. Tartakoff (1999)
J. Biol. Chem. 274, 33785-33789
   Abstract »    Full Text »    PDF »
SYK Is Upstream of Phosphoinositide 3-Kinase in B Cell Receptor Signaling.
L. O. Beitz, D. A. Fruman, T. Kurosaki, L. C. Cantley, and A. M. Scharenberg (1999)
J. Biol. Chem. 274, 32662-32666
   Abstract »    Full Text »    PDF »
Dependence of Dbl and Dbs Transformation on MEK and NF-kappa B Activation.
I. P. Whitehead, Q. T. Lambert, J. A. Glaven, K. Abe, K. L. Rossman, G. M. Mahon, J. M. Trzaskos, R. Kay, S. L. Campbell, and C. J. Der (1999)
Mol. Cell. Biol. 19, 7759-7770
   Abstract »    Full Text »    PDF »
Biological and Regulatory Properties of Vav-3, a New Member of the Vav Family of Oncoproteins.
N. Movilla and X. R. Bustelo (1999)
Mol. Cell. Biol. 19, 7870-7885
   Abstract »    Full Text »    PDF »
A Novel Role for H-Ras in the Regulation of Very Late Antigen-4 Integrin and VCAM-1 Via c-Myc-Dependent and -Independent Mechanisms.
Z.-J. Liu, Y. Tanaka, H. Fujimoto, S. Mine, A. Morinobu, H. Yagita, K. Okumura, I. Oishi, J. Udagawa, H. Yamamura, et al. (1999)
J. Immunol. 163, 4901-4908
   Abstract »    Full Text »    PDF »
Ras Proteins: Recent Advances and New Functions.
A. Rebollo and C. Martinez-A (1999)
Blood 94, 2971-2980
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Involvement of NH2-terminal Sequences in the Negative Regulation of Vav Signaling and Transforming Activity.
K. Abe, I. P. Whitehead, J. P. O'Bryan, and C. J. Der (1999)
J. Biol. Chem. 274, 30410-30418
   Abstract »    Full Text »    PDF »


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