Identification of Major Tyrosine Phosphorylation Sites in the Human Insulin Receptor Substrate Gab-1 by Insulin Receptor Kinase in Vitro†

Biochemistry ◽  
2000 ◽  
Vol 39 (35) ◽  
pp. 10898-10907 ◽  
Author(s):  
Stefan Lehr ◽  
Jörg Kotzka ◽  
Armin Herkner ◽  
Albert Sikmann ◽  
Helmut E. Meyer ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Human Insulin ◽  
Insulin Receptor Substrate ◽  
Phosphorylation Sites ◽  
Receptor Kinase ◽  
Human Insulin Receptor ◽  
Insulin Receptor Kinase

scholarly journals The Drosophila insulin receptor activates multiple signaling pathways but requires insulin receptor substrate proteins for DNA synthesis.

1996 ◽  
Vol 16 (5) ◽  
pp. 2509-2517 ◽  
Author(s):  
L Yenush ◽  
R Fernandez ◽  
M G Myers ◽  
T C Grammer ◽  
X J Sun ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Human Insulin ◽  
Mammalian Cells ◽  
Insulin Response ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Receptor Substrate ◽  
Human Insulin Receptor ◽  
Irs Proteins ◽  
Drosophila Insulin Receptor

The Drosophila insulin receptor (DIR) contains a 368-amino-acid COOH-terminal extension that contains several tyrosine phosphorylation sites in YXXM motifs. This extension is absent from the human insulin receptor but resembles a region in insulin receptor substrate (IRS) proteins which binds to the phosphatidylinositol (PI) 3-kinase and mediates mitogenesis. The function of a chimeric DIR containing the human insulin receptor binding domain (hDIR) was investigated in 32D cells, which contain few insulin receptors and no IRS proteins. Insulin stimulated tyrosine autophosphorylation of the human insulin receptor and hDIR, and both receptors mediated tyrosine phosphorylation of Shc and activated mitogen-activated protein kinase. IRS-1 was required by the human insulin receptor to activate PI 3-kinase and p70s6k, whereas hDIR associated with PI 3-kinase and activated p70s6k without IRS-1. However, both receptors required IRS-1 to mediate insulin-stimulated mitogenesis. These data demonstrate that the DIR possesses additional signaling capabilities compared with its mammalian counterpart but still requires IRS-1 for the complete insulin response in mammalian cells.

scholarly journals The in vitro synthesized and processed human insulin receptor precursor binds insulin

FEBS Letters ◽  
1999 ◽  
Vol 457 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Shawn Tsuda ◽  
Masahiro Kaihara ◽  
Xiangjun Zhou ◽  
Dean Britos ◽  
Richard Arakaki
Keyword(s):  
Insulin Receptor ◽  
Human Insulin ◽  
Human Insulin Receptor
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