Acylation of Gα13 is important for its interaction with thrombin receptor, transforming activity and actin stress fiber formation

FEBS Letters

Adarichev, Vyacheslav¹  Offermanns, Stefan³  Behn, Holger²  Ponimaskin, Evgeni²  Schmidt, Michael F.G.²  Voyno-Yasenetskaya, Tatyana A.¹ 

[1] University of Illinois, College of Medicine, Department of Pharmacology (MC 868), 835 S. Wolcott Ave, Chicago, IL 60612, USA;Institut für Immunologie und Molekularbiologie, Freie Universität Berlin, Philippstrasse 13, D-10115 Berlin, Germany;Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69/73, D-14195 Berlin, Germany

关键词: Palmitoylation;    Thrombin receptor;    Actin stress;    Fiber;    Gα12 protein;   

DOI  :  10.1016/S0014-5793(00)01845-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Palmitoylation of α-subunits in heterotrimeric G proteins has become a research object of growing attention. Following our recent report on the acylation of the mono-palmitoylated Gα₁₂ [Ponimaskin et al., FEBS Lett. 429 (1998) 370–374], we report here on the identification of three palmitoylation sites in the second member of the G₁₂ family, Gα₁₃, and on the biological significance of fatty acids on the particular sites. Using mutants of α₁₃ in which the potentially palmitoylated cysteine residues (Cys) were replaced by serine residues, we find that Cys-14, Cys-18 and Cys-37 all serve as palmitoylation sites, and that the mutants lacking fatty acids are functionally defective. The following biological functions of Gα₁₃ were found to be inhibited: coupling to the PAR1 thrombin receptor, cell transformation and actin stress fiber formation. Results from established assays for the above functions with a series of mutants, including derivatives of the constitutively active mutant Gα₁₃Q226L, revealed a graded inhibitory response on the above mentioned parameters. As a rule, it appears that palmitoylation of the N-proximal sites (e.g. Cys-14 and Cys-18) contributes more effectively to biological function than of the acylation site located more internally (Cys-37). However, the mutant with Cys-37 replaced by serine is more severely inhibited in stress fiber formation (80%) than in cell transformation (50%), pointing to the possibility of a differential involvement of the three palmitoylation sites in Gα₁₃.

【 授权许可】

Unknown