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Insulin activates a p21-activated kinase in muscle cells via phosphatidylinositol 3-kinase.

Authors: Tsakiridis, T  Taha, C  Grinstein, S  Klip, A 
Citation: Tsakiridis T, etal., J Biol Chem. 1996 Aug 16;271(33):19664-7.
Pubmed: (View Article at PubMed) PMID:8702668

Insulin activates rapidly a complex cascade of lipid and protein kinases leading to stimulation of mitogenic and metabolic events. Here we describe a renaturable kinase of 65 kDa (PK65) that becomes rapidly activated by insulin in differentiated L6 muscle cells (myotubes) and can phosphorylate histones immobilized in polyacrylamide gels. Insulin activation of PK65 was abolished by the tyrosine kinase inhibitor erbstatin and by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin, but was unaffected by inhibitors of protein kinase C or of the activation of p70(S6K). Recently, a number of protein kinases have been described which become activated through interaction with the small GTP-binding proteins Rac and Cdc42 (21-ctivated inases, or PAKs) and lead to activation of the stress-induced mitogen-activated protein kinase (MAPK) p38 MAPK. Two different polyclonal antibodies recognizing the carboxyl-terminal or the Rac-binding domain of a 65-kDa PAK (PAK65) immunoprecipitated the myotube PK65. The insulin-induced activation of PK65 in myotubes was detectable following immunoprecipitation of the kinase. Furthermore, PK65 associated with and became activated by glutathione S-transferase-Cdc42Hs in the presence of GTPgammaS (guanosine 5'-3-O-(thio)triphosphate). In myotubes insulin also induced tyrosine phosphorylation of p38 MAPK. However, this phosphorylation was insensitive to wortmannin, indicating that p38 MAPK is not activated by PK65 in insulin-stimulated cells. The results suggest that insulin activates in muscle cells a renaturable kinase (PK65) closely related to PAK65. Tyrosine kinases and PI 3-kinase act upstream of PK65 in the insulin signaling cascade. Insulin activates p38 MAPK in myotubes, but this occurs by a pathway independent of PI 3-kinase and PK65.

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CRRD Object Information
CRRD ID: 2299859
Created: 2008-08-18
Species: All species
Last Modified: 2008-08-18
Status: ACTIVE



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