Phospholipase C‐γ, protein kinase C and Ca2+/calmodulin‐dependent protein kinase II are involved in platelet‐derived growth factor‐induced phosphorylation of Tiam1

FEBS Letters

Exton, John H.¹  Elliott, Cassondra M.¹  Fleming, Ian N.¹ 

[1] Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

关键词: Platelet-derived growth factor;    Tiam1;    Phosphorylation;    Protein kinase C;    Protein kinase II;    Phospholipase C-γ;    DMEM;    Dulbecco's modified Eagle's medium;    EGF;    epidermal growth factor;    LPA;    lysophosphatidic acid;    PBS;    phosphate-buffered saline;    PDGF;    platelet-derived growth factor;    PIP2;    phosphatidylinositol 4;    5-bisphosphate;    PIP3;    phosphatidylinositol 3;    4;    5-trisphosphate;    PKC;    protein kinase C;    PLC;    phospholipase C;    PI 3-kinase;    phosphatidylinositol 3-kinase;    PMA;    phorbol 12-myristate 13-acetate;    RIPA buffer;    radioimmune precipitation buffer;   

DOI  :  10.1016/S0014-5793(98)00566-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In Swiss 3T3 fibroblasts, the Rac1-specific guanine nucleotide exchange factor Tiam1 is phosphorylated by several different agonists. We show here that PDGF induces threonine phosphorylation of Tiam1 in a time- and dose-dependent manner. Tiam1 phosphorylation was significantly reduced by the selective protein kinase C inhibitor Ro-31-8220 and by KN93, an inhibitor of Ca²⁺/calmodulin-dependent protein kinase II. The Ca²⁺ chelator BAPTA/AM totally abrogated Tiam1 phosphorylation, indicating that Ca²⁺ is essential for this phosphorylation. Moreover, PDGF-stimulated Tiam1 phosphorylation was markedly reduced by 72±10% in PLC-γ1 deficient mouse fibroblasts, compared to wild-type cells, indicating that phosphoinositide phospholipase C is involved.

【 授权许可】

Unknown