PKCalpha reduces the lipid kinase activity of the p110alpha/p85alpha PI3K through the phosphorylation of the catalytic subunit.
The modulation of phosphoinositide 3-kinase (PI3K) activity influences the quality of cellular responses triggered by various receptor tyrosine kinases. Protein kinase C (PKC) has been reported to phosphorylate signalling molecules upstream of PI3K and thereby it may affect the activation of PI3K. Here, we provide the first evidence for a direct effect of a PKC isoenzyme on the activity of PI3K. PKCalpha but not PKCepsilon phosphorylated the catalytic subunit of the p110alpha/p85alpha PI3K in vitro in a manner inhibited by the PKC inhibitor bisindolylmaleimide I (BIM I). The incubation of PI3K with active PKCalpha resulted in a significant decrease in its lipid kinase activity and this effect was also attenuated by BIM I. We conclude that PKCalpha is able to modulate negatively the lipid kinase activity of the p110alpha/p85alpha PI3K through the phosphorylation of the catalytic subunit.
Sipeki
Szabolcs
S
Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry 9 Puskin St., Budapest, Hungary. sipeki@puskin.sote.hu
Bander
Erzsébet
E
Parker
Peter J
PJ
Faragó
Anna
A
D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism
D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D019869:Phosphatidylinositol 3-Kinases; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; C070515:bisindolylmaleimide I