cAMP stimulates protein kinase B in a Wortmannin‐insensitive manner

FEBS Letters

Hemmings, Brian²  Filippa, Nathalie¹  Sable, Carol L¹  Van Obberghen, Emmanuel¹ 

[1] Institut National de la Santé et de la Recherche Médicale (INSERM) U 145, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cédex 2, France;Friedrich Miescher Institute, CH 4002 Basel, Switzerland

关键词: PKB;    cAMP;    PI3-kinase;    Phosphorylation;    bFGF;    basic fibroblast growth factor;    CPT–cAMP;    8-(4-cholorophenylthio)-cyclic AMP;    EGF;    epidermal growth factor;    GSK-3;    glycogen synthase kinase-3;    IGF-1;    insulin-like growth factor-1;    MAP kinase;    mitogen-activated protein kinase;    PDGF;    platelet-derived growth factor;    PGE1;    prostaglandin E1;    PH domain;    pleckstrin homology domain;    PI3-kinase;    phosphatidylinositol 3′-kinase;    PKA;    cAMP-dependent protein kinase;    PKB;    protein kinase B;    PKB-CA;    protein kinase B constitutively active;    p70S6k;    p70 ribosomal S6 protein kinase;   

DOI  :  10.1016/S0014-5793(97)00518-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Activation of protein kinase B (PKB) by growth factors has been demonstrated to proceed via phosphatidylinositol 3-kinase (PI3-kinase). Here, we show that agents which raise intracellular cAMP can also stimulate PKB. However, this effect is not sensitive to wortmannin, indicating that it is PI3-kinase independent. This activation does not appear to result from direct phosphorylation by protein kinase A (PKA) since GST–PKB is not an effective PKA substrate. In addition, the activation pathway of PKB by cAMP seems to be linked to that of growth factors, albeit downstream of PI3-kinase. Evidence for this is that a constitutive active PKB, T308D, S473D, containing activating mutations in the serine and threonine residues which are phosphorylated subsequent to PI3-kinase activation, cannot be further stimulated by cAMP elevations. Hence, these data suggest that, in addition to growth factors, cAMP can also lead to activation of PKB. This cAMP stimulatory action appears to require phosphorylation of T308 and S473, and hence would indicate that cAMP modulates the phosphorylation event of these PKB regulatory sites.

【 授权许可】

Unknown