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PMID: 15899863 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Tiam1-IRSp53 complex formation directs specificity of rac-mediated actin cytoskeleton regulation.

Molecular and cellular biology ·Vol. 25 ·No. 11 ·2005-06-00 ·Pages 4602-14

Connolly BA, Rice J, Feig LA, Buchsbaum RJ

Abstract

The exchange factor Tiam1 regulates multiple cellular functions by activating the Rac GTPase. Active Rac has various effects in cells, including alteration of actin cytoskeleton and gene expression, via binding to and modulating the activity of diverse effector proteins. How individual Rac effectors are selected for activation and regulated in response to upstream signals is not well understood. We find that Tiam1 contributes to both of these processes by binding to IRSp53, an adaptor protein that is an effector for both Rac and Cdc42. Tiam1 directs IRSp53 to Rac signaling by enhancing IRSp53 binding to both active Rac and the WAVE2 scaffold. Moreover, Tiam1 promotes IRSp53 localization to Rac-induced lamellipodia rather than Cdc42-induced filopodia. Finally, IRSp53 depletion from cells prevents Tiam1-dependent lamellipodia induced by Tiam1 overexpression or platelet-derived growth factor stimulation. These findings indicate that Tiam1 not only activates Rac but also contributes to Rac signaling specificity through binding to IRSp53.

MeSH Terms
Actin Cytoskeleton/metabolism Animals Cells, Cultured Guanine Nucleotide Exchange Factors/analysis,genetics,metabolism Humans Mice Microfilament Proteins/metabolism Neoplasm Proteins Nerve Tissue Proteins/analysis,genetics,metabolism Proteins/analysis,genetics,metabolism Pseudopodia/chemistry,metabolism Rats T-Lymphoma Invasion and Metastasis-inducing Protein 1 Two-Hybrid System Techniques Wiskott-Aldrich Syndrome Protein Family cdc42 GTP-Binding Protein/metabolism rac GTP-Binding Proteins/metabolism
Chemicals
BAIAP2 protein, human Guanine Nucleotide Exchange Factors Microfilament Proteins Neoplasm Proteins Nerve Tissue Proteins Proteins T-Lymphoma Invasion and Metastasis-inducing Protein 1 TIAM1 protein, human Tiam1 protein, mouse Tiam1 protein, rat WASF2 protein, human Wiskott-Aldrich Syndrome Protein Family cdc42 GTP-Binding Protein rac GTP-Binding Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Connolly Beth A
The Department of Biochemistry, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA 02111, USA.
Rice Jared
Feig Larry A
Buchsbaum Rachel J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.11.4602-4614.2005
Published
2005-06-00
Pages
4602-14
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1140638
Subset
IM
Grants
NCI NIH HHS · CA95559 · United States
NIDDK NIH HHS · P30 DK034928 · United States
NCI NIH HHS · CA47391 · United States
NCI NIH HHS · R01 CA095559 · United States
NCI NIH HHS · R01 CA047391 · United States
NIDDK NIH HHS · P30-DK34928 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1128/MCB.25.11.4602-4614.2005 PMC Full Text View journal details
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