Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors

William T. Arthur, Lawrence Quilliam, Jonathan A. Cooper

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading in various mammalian cell types. Here, we demonstrate that Rap1 regulates cell spreading by localizing guanine nucleotide exchange factors (GEFs) that act via the Rho family GTPase Rac1. Rap1a activates Rac1 and requires Rac1 to enhance spreading, whereas Rac1 induces spreading independently of Rap1. Active Rap1a binds to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as SWAP-70 or COOL-1. Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1. Rap1 is necessary for the accumulation of VAV2 in membrane protrusions at the cell periphery. In addition, if VAV2 is artificially localized to the cell edge with the subcellular targeting domain of Rap1a, it increases cell spreading independently of Rap1. These results lead us to propose that Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension.

Original languageEnglish
Pages (from-to)111-122
Number of pages12
JournalJournal of Cell Biology
Volume167
Issue number1
DOIs
StatePublished - Oct 11 2004

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Guanine Nucleotide Exchange Factors
Cell Surface Extensions
rho GTP-Binding Proteins
Pseudopodia
Monomeric GTP-Binding Proteins
Integrins
Catalytic Domain

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. / Arthur, William T.; Quilliam, Lawrence; Cooper, Jonathan A.

In: Journal of Cell Biology, Vol. 167, No. 1, 11.10.2004, p. 111-122.

Research output: Contribution to journalArticle

Arthur, William T. ; Quilliam, Lawrence ; Cooper, Jonathan A. / Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. In: Journal of Cell Biology. 2004 ; Vol. 167, No. 1. pp. 111-122.
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