Regulation of Cbl-associated protein/Cbl pathway in muscle and adipose tissues of two animal models of insulin resistance
Authors: Lício A Velloso
José B C Carvalheira
Aparecida E Hirata
Mario J A Saad
Ana C P Thirone
Journal: Endocrinology (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: phosphatidylinositol 3-kinase; glucose transport; tyrosine phosphorylation; c-Cbl; insulin
Affiliations: Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13081-970 Campinas, São Paulo, Brazil., Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13081-970 Campinas, São Paulo, Brazil

Abstract:  The phosphatidylinositol 3-kinase-independent pathway to induce glucose transport may involve the tyrosine phosphorylation of the protooncogene c-Cbl. In the present study, we examined whether acute exposure to insulin stimulates the tyrosine phosphorylation of Cbl and its association with Cbl-associated protein (CAP) in muscle and adipose tissue of rats in vivo. We report herein that insulin induces Cbl tyrosine phosphorylation and association with CAP in adipose tissue but not in muscle. We also examined the expression and tyrosyl-phosphorylation state of Cbl and CAP/Cbl association in adipose tissue of rats submitted to prolonged fasting and in monosodium glutamate (MSG)-insulin-resistant rats. An increase in Cbl phosphorylation is observed in the fat of MSG rats, parallel with an increase in association of CAP-Cbl as well as an augment in CAP and Cbl protein expression in the adipose tissue of these animals. These events are accompanied by a decrease in insulin-stimulated insulin receptor/ insulin receptor substrate (IRS)-1 tyrosine phosphorylation and an increase in the IRS-2/phosphatidylinositol 3-kinase/Akt/Foxo1 pathway. In adipocytes of fasted rats, there is a decrease in CAP and Cbl protein expression, insulin-induced Cbl phosphorylation, and the association with CAP. In parallel, there is also a decrease in the insulin receptor/IRSs/Akt/Foxo1 pathway. Thus, insulin is able to induce Cbl tyrosine phosphorylation and its association with CAP in the adipose tissue of normal rats. In addition, our data provide evidence that the CAP-Cbl pathway may have a role in the modulation of adiposity in fasting and in MSG-treated rats. 

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 #4 In Fig. 2C of Febs let article, bands # 1 and # 5 are also identical. , 
 #4 I just noticed something very unusual: the two graphs pointed out by  #4 Unregistered (Fig.5 endocrinology and Figure 2 Febs lett) are identical to the two graphs listed earlier by  #2 unregistered (Fig. 5 and Fig. 1). The blots are different, but the graphs clearly the same! , 
 The introduction of this article  THE INSULIN RECEPTOR is a tyrosine kinase that catalyzes the phosphorylation of several intracellular substrates, including the insulin receptor substrate (IRS) proteins, GAB-1, Shc, APS, p60DOK, SIRPS, and c-Cbl (1u20137). Each of these substrates recruits a distinct subset of signaling proteins containing Src homology 2 (SH2) domains, which interact specifically with sequences surrounding the phosphotyrosine residue . is plagiarized from Saltiel and Pessin, 2002 (PMID: 11849969):  The insulin receptor is a tyrosine kinase that catalyzes the phosphorylation of several intracellular substrates, including the insulin receptor substrate (IRS) proteins [2], GAB-1 [3], Shc [4], APS [5], p60DOK [6], SIRPS [7] and c-Cbl [8] (Fig. 1). Each of these substrates recruits a distinct subset of signaling proteins containing Src homology 2 (SH2) domains, which interact specifically with sequences surrounding the phosphotyrosine residue.  ,