The tetraspanin CD151 functions as a negative regulator in the adhesion-dependent activation of Ras

Shigeaki Sawada, Mitsunori Yoshimoto, Elena Odintsova, Neil A Hotchin, Fedor Berditchevski

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Transmembrane proteins of the tetraspanin superfamily are associated with integrins and are thought to regulate adhesion-dependent signaling. The molecular mechanisms of this regulation remain unknown. We used rat fibroblasts to analyze the contribution of the tetraspanin CD151 in the adhesion-dependent signaling. Expression of CD151 specifically attenuated adhesion-dependent activation of Ras. Furthermore, activation of PKB/c-Akt and ERK1/2, downstream targets in the Ras signaling pathway, was also diminished in cells expressing CD151. In contrast, adhesion-dependent activation of FAK and c-Src were not affected by CD151. The attenuation of Ras signaling did not correlate with phosphorylation of Tyr925-FAK, tyrosine phosphorylation of Shc, or with assembly of the p120RasGAP-p62Dok complex. Using mutants of CD151 we established that the cytoplasmic C-terminal portion is critical for activity of CD151 toward Ras. Taken together these results identify CD151 as a negative regulator of Ras and suggest a novel mechanism of adhesion-dependent regulation of Ras activity.
Original languageEnglish
Pages (from-to)26323-26326
Number of pages4
JournalJournal of Biological Chemistry
Volume278
Issue number29
Early online date22 May 2003
DOIs
Publication statusPublished - 2003

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