Gβγ subunits stimulate p21‐activated kinase 1 (PAK1) through activation of PI3‐kinase and Akt but act independently of Rac1/Cdc42

FEBS Letters

Mattingly, Raymond R¹  Menard, Raymond E¹ 

[1] Department of Pharmacology, Wayne State University, 540 East Canfield Avenue, Room 6326, Detroit, MI 48201, USA

关键词: p21-Activated kinase;    G protein-coupled receptor;    Serine–threonine kinase;    PAK;    p21-activated kinase;    MBP;    myelin basic protein;    LPA;    lysophosphatidic acid;    EGF;    epidermal growth factor;    PMA;    phorbol 12-myristate 13-acetate;    MAPK;    mitogen-activated protein kinase;    HA;    haemagglutinin;    PI3-kinase;    phosphoinositide 3-kinase;    CRIB domain;    Cdc42/Rac-interactive binding domain;    AID;    autoinhibitory domain;   

DOI  :  10.1016/S0014-5793(03)01406-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The p21-activated kinase (PAK) family is homologous to the yeast sterile 20 (Ste20) and regulates a wide variety of cellular responses, including cell morphology, proliferation, and survival. In this study we examined the activation of PAK1 by Gβγ subunits. Co-transfection of COS7 cells with Gβ1γ2 or Gβ1γ5 was sufficient to induce agonist-independent activation of PAK1. Expression of dominant/negative Rac, Cdc42, or Ras did not inhibit this Gβγ-dependent activation. Wortmannin, which inhibits phosphoinositide 3-kinase (PI3-kinase) activity, and expression of a dominant/negative form of Akt were sufficient to abrogate the activation of PAK1 that was induced by Gβγ. These results reveal that stimulation of PAK1 by Gβγ can occur via a PI3-kinase and Akt pathway that does not require Rac1 or Cdc42.

【 授权许可】

Unknown