This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sajan, M. P. Articles by Farese, R. V. Search for Related Content PubMed PubMed Citation Articles by Sajan, M. P. Articles by Farese, R. V.

Tissue-Specific Differences in Activation of Atypical Protein Kinase C and Protein Kinase B in Muscle, Liver, and Adipocytes of Insulin Receptor Substrate-1 Knockout Mice

Research Service (M.P.S., M.L.S., A.M., R.V.F.), James A. Haley Veterans Hospital and the Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida 33612; and the Research Division (C.R.K.), Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Robert V. Farese, M.D., James A. Haley Veterans Hospital, ACOS-151, 13000 Bruce B. Downs Boulevard, Tampa, Florida 33612. E-mail: rfarese{at}hsc.usf.edu.

Insulin receptor substrates (IRSs) 1 and 2 are postulated to control the activation of phosphatidylinositol 3-kinase (PI3K)-dependent signaling factors, namely, atypical protein kinase C (aPKC) and protein kinase B (PKB)/Akt, which mediate metabolic effects of insulin. However, it is uncertain whether aPKC and PKB are activated together or differentially in response to IRS-1 and IRS-2 activation in insulin-sensitive tissues. Presently, we examined insulin activation of aPKC and PKB in vastus lateralis muscle, adipocytes, and liver in wild-type and IRS-1 knockout mice, and observed striking tissue-specific differences. In muscle of IRS-1 knockout mice, the activation of both aPKC and PKB was markedly diminished. In marked contrast, only aPKC activation was diminished in adipocytes, and only PKB activation was diminished in liver. These results suggest that IRS-1 is required for: 1) activation of both aPKC and PKB in muscle; 2) aPKC, but not PKB, activation in adipocytes; and 3) PKB, but not aPKC, activation in liver. Presumably, IRS-2 or other PI3K activators account for the normal activation of aPKC in liver and PKB in adipocytes of IRS-1 knockout mice. These complexities in aPKC and PKB activation may be relevant to metabolic abnormalities seen in tissues in which IRS-1 or IRS-2 is specifically or predominantly down-regulated.

This article has been cited by other articles:

				H. Sharfi and H. Eldar-Finkelman Sequential phosphorylation of insulin receptor substrate-2 by glycogen synthase kinase-3 and c-Jun NH2-terminal kinase plays a role in hepatic insulin signaling Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E307 - E315. [Abstract] [Full Text] [PDF]

				R. A. Frost and C. H. Lang Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass J Appl Physiol, July 1, 2007; 103(1): 378 - 387. [Abstract] [Full Text] [PDF]

				R. V. Farese, M. P. Sajan, and M. L. Standaert Insulin-Sensitive Protein Kinases (Atypical Protein Kinase C and Protein Kinase B/Akt): Actions and Defects in Obesity and Type II Diabetes Experimental Biology and Medicine, October 1, 2005; 230(9): 593 - 605. [Abstract] [Full Text] [PDF]