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3BP-1, an SH3 domain binding protein, has GAP activity for Rac and inhibits growth factor-induced membrane ruffling in fibroblasts

Cicchetti, Piera and Ridley, Anne J. and Zheng, Yi and Cerione, Richard A. and Baltimore, David (1995) 3BP-1, an SH3 domain binding protein, has GAP activity for Rac and inhibits growth factor-induced membrane ruffling in fibroblasts. EMBO Journal, 14 (13). pp. 3127-3135. ISSN 0261-4189. PMCID PMC394374. doi:10.1002/j.1460-2075.1995.tb07315.x.

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The SH3 binding protein, 3BP‐1, was originally cloned as a partial cDNA from an expression library using the Abl SH3 domain as a probe. In addition to an SH3 binding domain, 3BP‐1 displayed homology to a class of GTPase activating proteins (GAPs) active against Rac and Rho proteins. We report here a full length cDNA of 3BP‐1 which extends the homology to GAP proteins previously noted. 3BP‐1 functions in vitro as a GAP with a specificity for Rac‐related G proteins. Microinjection of the 3BP‐1 protein into serum‐starved fibroblasts produces an inhibition of platelet‐derived growth factor (PDGF)‐induced membrane ruffling mediated by Rac. Co‐injection of 3BP‐1 with an activated Rac mutant that is unresponsive to GAPs, counter‐acts this inhibition. 3BP‐1 does not show in vitro activity towards Rho and, in agreement with this finding, microinjection of 3BP‐1 into fibroblasts has no effect on lysophosphatidic acid (LPA)‐induced stress fiber assembly mediated by Rho. Thus 3BP‐1 is a new and specific Rac GAP that can act in cells to counter Rac‐mediated membrane ruffling. How its SH3 binding site interacts with its GAP activity remains to be understood.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 1995 European Molecular Biology Organization. Published: 3 July 1995. We thank Matthew J. Hart for initial in vitro GAP assays, Ritu Garg for excellent assistance with cell culture, Ruibao Ren for help in isolating the 3BP-1 cDNA clone, David Schatz for the λgt10 library and Gerald Thiel for advice and support. This work was supported by the National Research Service Award training grant CA 09673 (P.C.) and the US Public Health Service grant CA 51462 (D.B.). Accession number: The sequence reported in this paper has been deposited in the EMBL database under accession number X87671.
Funding AgencyGrant Number
NIH Predoctoral FellowshipCA09673
Subject Keywords:cytoskeleton; GAP; Rac; SH3; 3BP-I
Issue or Number:13
PubMed Central ID:PMC394374
Record Number:CaltechAUTHORS:20200512-102418759
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103134
Deposited By: Tony Diaz
Deposited On:12 May 2020 18:48
Last Modified:16 Nov 2021 18:18

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