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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-stimulated glucose transport in adipocytes is mediated by the insulin receptor. To ascertain whether a related receptor could also trigger this response, the epidermal growth factor (EGF) receptor (EGFR) was introduced into adipocytes. 3T3-L1 fibroblasts were infected by a retroviral construct encoding either the full-length (WT) or a carboxy-terminal truncated (c'973) human EGFR; truncation of the amino acids distal to 973 removes all autophosphorylation motifs. After selection and conversion to adipocytes, the level of EGFR expression was retained in infectant adipocytes (150,000 and 250,000/cell, respectively), but not in the parental 3T3-L1 adipocytes (< 5000/cell). WT and c'973 EGFR exhibited ligand-dependent tyrosine kinase activity and stimulated mitogen-activated protein kinase activity equivalently; neither phosphorylated insulin receptor substrate-1. WT EGFR, but not c'973 EGFR, underwent ligand-induced autophosphorylation. EGF did not stimulate tyrosine phosphorylation of the insulin receptor or insulin receptor substrate-1. EGF had a minimal effect on glucose transport by parental 3T3-L1 adipocytes. Glucose transport in the WT EGFR adipocytes was stimulated equivalently by insulin and EGF; exposure to insulin and EGF in combination did not result in augmented transport. Glucose transport in the c'973 EGFR adipocytes was stimulated by insulin, but not by EGF. GLUT4 was translocated to the plasma membrane to a similar extent in response to insulin or EGF in the WT EGFR adipocytes; only insulin caused a significant GLUT4 translocation in the parental or c'973 EGFR adipocytes. These data suggest that the insulin and EGF signaling pathways that lead to glucose transport converge in these adipocytes down-stream of the insulin receptor, and that activation of this pathway requires signaling motifs in the carboxy-terminus of the EGFR. This model system represents a novel approach with which to dissect signal transduction pathways in terminally differentiated adipocytes.
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PMID:Epidermal growth factor (EGF) receptor carboxy-terminal domains are required for EGF-induced glucose transport in transgenic 3T3-L1 adipocytes. 783 73

Overexpression of surrogate receptors [epidermal growth factor (EGF) receptor (EGFR) and platelet-derived growth factor receptor] in adipocytes has demonstrated that multiple signaling pathways may lead to GLUT4-mediated glucose uptake. These implicated pathways function independently of IRS-1 phosphorylation and PI3-kinase activation. In addition, we previously demonstrated that EGFR tyrosyl autophosphorylation is required to stimulate GLUT4-mediated glucose transport in 3T3-L1 adipocytes. This observation suggests that signaling molecules that are dependent on EGFR autophosphorylation, such as phospholipase C (PLC), may lie in the signaling pathway to glucose transport. As PLC has been implicated in glucose transport by several clinical and basic mechanistic studies, we investigated whether EGFR signaling may promote glucose transport via modulation of PLC activity. Activation of EGFR overexpressing 3T3-L1 adipocytes leads to a 3.4 +/- 1.2-fold stimulation of PLC activity over basal levels vs. only 1.06 +/- 0.01-fold stimulation by insulin. Pharmacological inhibition of PLC by 50 microM U73122 reduced phosphoinositide accumulation by 79.2 +/- 16.9% and resulted in a concomitant 56.0 +/- 12.7% decrease in EGF-induced glucose transport. This inhibition of glucose transport by U73122 was specific, because the inactive congener, U73343, failed to block EGF-induced glucose transport. Despite the low levels of insulin-induced PLC activity, insulin-stimulated glucose transport activity was similarly inhibited by U73122 (55.9 +/- 13.1% inhibition). Inhibition of PLC activation did not impair either EGF- or insulin-induced activation of glycogen synthase or incorporation of glucose into lipid, supporting the hypothesis that both EGF- and insulin-induced glucose disposal can be independent of GLUT4-mediated glucose transport. The diminution of glucose transport secondary to inhibition of PLC activity was reflected by a decrease in GLUT4 translocation to the plasma membrane upon either EGF or insulin stimulation. These results are consistent with either a permissive or an active role for PLC activity in the translocation of GLUT4 to the plasma membrane.
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PMID:A role for phospholipase C activity in GLUT4-mediated glucose transport. 938 97