期刊
JOURNAL OF CELL SCIENCE
卷 123, 期 8, 页码 1306-1319出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.062570
关键词
Gab1; RTK; Dorsal ruffles; Nck; N-WASP; Morphogenesis; Actin
类别
资金
- US Department of Defence Breast Cancer Research Initiative [DAMD17-99-1-9284]
- Fonds de recherche en sante du Quebec
- Canadian Institutes of Health Research (CIHR)
- Richard H. Tomlinson Doctoral Fellowship
- Cancer Research Society
- Terry Fox Foundation
- National Cancer Institute of Canada
- Canadian Cancer Society
The polarised distribution of signals downstream from receptor tyrosine kinases RTKs) regulates fundamental cellular processes that control cell migration, growth and morphogenesis. It is poorly understood how RTKs are involved in the localised signalling and actin remodelling required for these processes. Here, we show that the Gab1 scaffold is essential for the formation of a class of polarised actin microdomain, namely dorsal ruffles, downstream from the Met, EGF and PDGF RTKs. Gab1 associates constitutively with the actin-nucleating factor N-WASP. Following RTK activation, Gab1 recruits Nck, an activator of N-WASP, into a signalling complex localised to dorsal ruffles. Formation of dorsal ruffles requires interaction between Gab1 and Nck, and also requires functional N-WASP. Epithelial cells expressing Gab1 Delta Nck Y407F) exhibit decreased Met-dependent Rac activation, fail to induce dorsal ruffles, and have impaired cell migration and epithelial remodelling. These data show that a Gab1-Nck signalling complex interacts with several RTKs to promote polarised actin remodelling and downstream biological responses.
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