Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors

Journal of Cell Biology - Tập 167 Số 1 - Trang 111-122 - 2004
William T. Arthur1, Lawrence A. Quilliam2, Jonathan A. Cooper3
1Fred Hutchison Cancer Research Center, Seattle, WA 98109, USA
22Department of Biochemistry and Molecular Biology and Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN 46202
31Fred Hutchinson Cancer Research Center, Seattle, WA 98109

Tóm tắt

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.

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Thông tin xuất bản

Journal of Cell Biology

Tập 167 Số 1

111-122

Thông tin tác giả