Insulin Induces Tyrosine Phosphorylation of Shc and Stimulates Shc/GRB2 Association in Insulin-Sensitive Tissues of the Intact Rat

Paez-Espinosa, Veronica; Carvalho, Carla Roberta de Oliveira; Alvarez-Rojas, Fernanda; Janeri, Luis; Velloso, Lı́cio A.; Boschero, Antônio Carlos; Saad, Mário José Abdalla

doi:10.1385/endo:8:2:193

Cited by 19 publications

(15 citation statements)

References 37 publications

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“…Shc and ERK-1/2 phosphorylation Consistent with previous reports [26,27], we found no detectable phosphorylation in the p46 and p66 isoforms of Shc. As shown in Fig.…”

Section: Akt Activationsupporting

confidence: 93%

Irbesartan restores the in-vivo insulin signaling pathway leading to Akt activation in obese Zucker rats

Muñoz

Argentino

Dominici

et al. 2006

Journal of Hypertension

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“…Shc and ERK-1/2 phosphorylation Consistent with previous reports [26,27], we found no detectable phosphorylation in the p46 and p66 isoforms of Shc. As shown in Fig.…”

Section: Akt Activationsupporting

confidence: 93%

Irbesartan restores the in-vivo insulin signaling pathway leading to Akt activation in obese Zucker rats

Muñoz

Argentino

Dominici

et al. 2006

Journal of Hypertension

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“…Furthermore, there is a kinase activity of the insulin receptor towards immunopurified Shc. We have previously demonstrated that insulin induces Shc tyrosine phosphorylation in rat tissues, and a kinase activity of the insulin receptor towards Shc was also suggested (15). The results presented here clearly demonstrate that the insulin receptor is able to induce tyrosine phosphorylation of immunopurified Shc.…”

supporting

confidence: 74%

“…By immunoblotting with specific antibodies it was previously demonstrated that these bands correspond to IRS-1 and IRS-2 which probably were bound to the insulin receptor after insulin stimulation (15).…”

mentioning

confidence: 98%

Insulin receptor has tyrosine kinase activity toward Shc in rat liver

Paez-Espinosa

Carvalho

Velloso

et al. 1998

Braz J Med Biol Res

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Insulin induces tyrosine phosphorylation of Shc in cell cultures and in insulin-sensitive tissues of the intact rat. However, the ability of insulin receptor (IR) tyrosine kinase to phosphorylate Shc has not been previously demonstrated. In the present study, we investigated insulin-induced IR tyrosine kinase activity towards Shc. Insulin receptor was immunoprecipitated from liver extracts, before and after a very low dose of insulin into the portal vein, and incubated with immunopurified Shc from liver of untreated rats. The kinase assay was performed in vitro in the presence of exogenous ATP and the phosphorylation level was quantified by immunoblotting with antiphosphotyrosine antibody. The results demonstrate that Shc interacted with insulin receptor after infusion of insulin, and, more important, there was insulin receptor kinase activity towards immunopurified Shc. The description of this pathway in animal tissue may have an important role in insulin receptor tyrosine kinase activity toward mitogenic transduction pathways.

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“…IRS proteins undergo marked tyrosine phosphorylation in response to stimulation of insulin receptors and thereby provide docking sites for PI 3-kinase and the protein-tyrosine phosphatase SHP-2, the latter of which upregulates Ras activity (43). Furthermore, insulin receptors phosphorylate the adapter molecule SHC (44), which is a potent activator of the Ras-mitogen-activated protein kinase pathway. These insulin receptor-evoked positive signals to Ras may therefore have masked Dok-1 regulation of Ras activity in the study of Noguchi et al (42).…”

Section: Resultsmentioning

confidence: 99%

Mediation by the Protein-tyrosine Kinase Tec of Signaling between the B Cell Antigen Receptor and Dok-1

Yoshida¹,

Yamashita²,

Miyazato³

et al. 2000

Journal of Biological Chemistry

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The protein-tyrosine kinase (PTK) 1 Tec was initially isolated from mouse liver (1) and was subsequently shown to be expressed in many tissues, including spleen, lung, brain, and kidney (2). Four Tec-related PTKs, including Btk (3, 4), Itk (also known as Emt or Tsk) (5-7), Bmx (8), and Txk (or Rlk) (9, 10), have since been molecularly cloned. With the exception of Txk, Tec and the Tec-related PTKs possess a relatively long NH 2 -terminal region that consists of a pleckstrin homology (PH) domain (11) and a Tec homology (TH) domain (12). The PH domain is thought to mediate protein binding to various phospholipids or phospholipid-derived molecules; for example, the Tec PH domain binds to phosphatidylinositol (PI) 3,4,5-trisphosphate (13), and the Btk PH domain binds to inositol 1,3,4,5-tetrakisphosphate (14) and PI 3,4,5-trisphosphate (15). These PH domain-phospholipid interactions are thought to mediate the conditional tethering of Tec family kinases to the cell membrane, suggesting that these enzymes might act downstream of PI 3-kinase. The TH domain of Tec PTKs contains proline-rich sequences that interact with the Src homology (SH) 3 domain of these same proteins (16) and, probably, also with the SH3 domains of other proteins. The intramolecular interaction between the TH and SH3 domains results in the bending of Tec proteins, which likely serve to mask their catalytic centers and to inhibit kinase activity.Several Tec proteins are abundant in hematopoietic tissues and are therefore thought to play important roles in the development or maintenance of the hematopoietic system. Indeed, Tec PTKs are activated in blood cells by stimulation of cytokine receptors, lymphocyte surface antigens, G protein-coupled receptors, receptor type PTKs, or integrins (17). Furthermore, a functional Btk is indispensable for the maturation of B lymphocytes and the subsequent production of immunoglobulins. However, the downstream effectors of Tec family kinases remain largely unknown. Tec, Btk, and Itk each phosphorylate and activate phospholipase C (PLC)-␥2 (18). Candidate substrates for Btk also include BAP-135 (or TFII-I) (19) and WASP (20) and those for Tec include Grb10 (21), BRDG1 (22), and Sak kinase. 2Stimulation of cell surface receptors often induces the tyrosine phosphorylation of two unidentified Tec-binding proteins in addition to that of Tec. One of these Tec-binding phosphoproteins, p62, gives rise to a broad blurred band of ϳ62-66 kDa on immunoblot analysis with antibodies to phosphotyrosine, suggesting that the protein is phosphorylated on multiple tyrosine residues. The other Tec-binding phosphoprotein migrates at a position corresponding to a molecular size of ϳ56 kDa. Tyrosine phosphorylation of p62 is induced by cross-linking of the B cell antigen receptor (BCR) in B lymphocytes (23) and by activation of c-Kit in myeloid cells (24). Immunoblot analysis indicates that p62 is not identical to Sam68 or SHC. The protein p62Dok-1 was isolated as a major substrate for activated Abl tyrosine kinases (25,26). Dok-1 conta...

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Insulin Induces Tyrosine Phosphorylation of Shc and Stimulates Shc/GRB2 Association in Insulin-Sensitive Tissues of the Intact Rat

Cited by 19 publications

References 37 publications

Irbesartan restores the in-vivo insulin signaling pathway leading to Akt activation in obese Zucker rats

Irbesartan restores the in-vivo insulin signaling pathway leading to Akt activation in obese Zucker rats

Insulin receptor has tyrosine kinase activity toward Shc in rat liver

Mediation by the Protein-tyrosine Kinase Tec of Signaling between the B Cell Antigen Receptor and Dok-1

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