Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells
Autor: | Joshua D Sparling, Valeria R. Fantin, Brian E. Lavan, Gustav E. Lienhard, Jan W. Slot, Susanna R. Keller |
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Rok vydání: | 1998 |
Předmět: |
Biology
Kidney Biochemistry Cell Line src Homology Domains chemistry.chemical_compound Insulin Receptor Substrate 4 Insulin receptor substrate Humans RNA Messenger Phosphorylation Growth Substances Microscopy Immunoelectron Molecular Biology Insulin-like growth factor 1 receptor Adaptor Proteins Signal Transducing GRB10 Tyrosine phosphorylation Cell Biology Phosphoproteins Molecular biology IRS2 Insulin receptor chemistry biology.protein Insulin Receptor Substrate Proteins Tyrosine GRB2 Subcellular Fractions |
Zdroj: | The Journal of biological chemistry. 273(17) |
ISSN: | 0021-9258 |
Popis: | We recently cloned IRS-4, a new member of the insulin receptor substrate (IRS) family. In this study we have characterized IRS-4 in human embryonic kidney 293 cells, where it was originally discovered. IRS-4 was the predominant insulin-elicited phosphotyrosine protein in these cells. Subcellular fractionation revealed that about 50% of IRS-4 was located in cellular membranes, and immunofluorescence indicated that IRS-4 was concentrated at the plasma membrane. Immunoelectron microscopy conclusively established that a large portion of the IRS-4 was located at the cytoplasmic surface of the plasma membrane in both the unstimulated and insulin-treated states. IRS-4 was found to be associated with two src homology 2 (SH2) domain-containing proteins, phosphatidylinositol 3-kinase and Grb2, the adaptor to the guanine nucleotide exchange factor for Ras. On the other hand, no significant association was detected with two other SH2 domain proteins, the SH2-containing protein tyrosine phosphatase 2 and phospholipase Cgamma. Insulin-like growth factor I acting through its receptor was as effective as insulin in eliciting tyrosine phosphorylation of IRS-4, but interleukin 4 and epidermal growth factor were ineffective. |
Databáze: | OpenAIRE |
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