Abstract

TrkA is a cell surface transmembrane receptor tyrosine kinase for nerve growth factor (NGF). TrkA has an NPXY motif and kinase regulatory loop similar to insulin receptor (INSR) suggesting that NGF→TrkA signaling might overlap with insulin→INSR signaling. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Moreover, expression of TrkA kinase-inactive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF. Based on these data, we propose that TrkA participates in insulin signaling pathway in PC12 cells.

Highlights

  • TrkA is a transmembrane receptor tyrosine kinase for nerve growth factor

  • We report that nerve growth factor (NGF) or insulin induces TrkA to form a molecular complex with insulin receptor (INSR) and insulin receptor substrate-1 (IRS-1)

  • The lysates were Western blotted with TrkA and insulin receptor substrate (IRS)-1 antibody to check their expression level (Fig. 2C). These results suggest that stimulation of PC12 cells with insulin or NGF leads to the association of TrkA receptor with IRS-1 and tyrosine phosphorylation of TrkA

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Summary

Introduction

TrkA is a transmembrane receptor tyrosine kinase for nerve growth factor. Results: TrkA forms a molecular complex with insulin receptor and IRS-1 to induce Akt and Erk5 phosphorylation. During insulin or NGF stimulation TrkA, insulin receptor substrate-1 (IRS-1), INSR (and presumably other proteins) forms a complex in PC12 cells. In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain.

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