Wortmannin and 1‐butanol block activation of a novel family of protein kinases in neutrophils

FEBS Letters

Badwey, John A.²  Ding, Jiabing¹ 

[1]Department Of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA

[2]Boston Biomedical Research Institute, 20 Staniford St., Boston, MA 02114, USA

关键词: Neutrophil: Cell signalling;    Protein kinase;    Superoxide;    fMLP;    fMet-Leu-Phe;    0− 2;    superoxide;    PMA;    4;    β-phorbol 12-myristate 13-acetate;    p47-phox;    the 47 kDa protein component of the phagocyte oxidase;    PI 3-kinase;    phosphatidylinositol 3-kinase;   

DOI  :  10.1016/0014-5793(94)00593-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Neutrophils contain four uncharacterized protein kinases with molecular masses of ca. 69, 63, 49 and 40 kDa that are rapidly activated upon stimulation of these cells with the chemoattractant fMet-Leu-Phe [Ding, J. and Badwey, J.A. (1993) J. Biol. Chem. 268, 17326–17333]. We now report that wortmannin and 1-butanol block activation of all four of these kinases. These reagents are known to inhibit superoxide generation in neutrophils stimulated with this agonist. Wortmannin inhibits phosphatidylinositol 3-kinase and blocks activation of phospholipase D, whereas 1-butanol can reduce the generation of phosphatidate in cells by serving as a substrate for phospholipase D. These data suggest that phosphatidylinositol 3-kinase and phospholipase D may be involved in the activation of several novel protein kinases in neutrophils and that one or more of these kinases is/are involved in superoxide release.

【 授权许可】

Unknown