Open AccessProtein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity.
Author(s) -
Gideon Bollag,
Richard A. Roth,
Jacqueline Beaudoin,
Daria MochlyRosen,
D E Koshland
Publication year - 1986
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.83.16.5822
Subject(s) - irs2 , mitogen activated protein kinase kinase , map2k7 , insulin receptor , cyclin dependent kinase 2 , cyclin dependent kinase 9 , biochemistry , map kinase kinase kinase , grb10 , protein kinase a , tropomyosin receptor kinase c , protein kinase c , ask1 , insulin receptor substrate , protein phosphorylation , biology , chemistry , phosphorylation , platelet derived growth factor receptor , insulin , receptor , endocrinology , insulin resistance , growth factor
The beta subunit of purified insulin receptor is phosphorylated on a serine residue by purified preparations of protein kinase C (ATP: protein phosphotransferase, EC 2.7.1.37). This phosphorylation is inhibited by antibodies to protein kinase C and stimulated by phospholipids, diacylglycerol, and Ca2+. The phosphorylation of the receptor by protein kinase C does not affect its insulin-binding activity but does inhibit by 65% the receptor's intrinsic tyrosine-specific protein kinase activity (ATP: protein-tyrosine O-phosphotransferase, EC 2.7.1.112). These results indicate that activators of protein kinase C, such as phorbol esters, desensitize cells to insulin by direct protein kinase C action on the insulin receptor.
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