Substrates and signalling complexes: the tortured path to insulin action.
In the last few years several potential substrates of the insulin receptor tyrosine kinase have been identified, purified, and their cDNAs isolated. These putative substrates include: 1) pp15, a fatty acid-binding protein; 2) pp120, a plasma membrane ecto-ATPase; 3) pp42, a MAP serine/threonine kinase; 4) pp85, a subunit of the Type 1 phosphatidylinositol kinase; and 5) pp185, a phosphatidylinositol kinase binding protein. Although the tyrosine phosphorylation of several of these substrates correlates with the signalling capabilities of various mutant receptors, the role of these substrates in mediating any one of insulin's many biological responses is still unknown. In addition, recent data indicate that the tyrosine phosphorylation of pp42 may in fact be due to autophosphorylation, thereby removing it from the list of putative substrates of the insulin receptor kinase. Finally, the present review discusses the question of whether signalling occurs as a result of the tyrosine phosphorylation of substrates or via the formation of signalling complexes.
Roth
R A
RA
Department of Pharmacology, Stanford University School of Medicine, California 94305.
Zhang
B
B
Chin
J E
JE
Kovacina
K
K
D019870:1-Phosphatidylinositol 4-Kinase; D000251:Adenosine Triphosphatases / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins; D014443:Tyrosine / Q000378:metabolism
D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D010770:Phosphotransferases; D011494:Protein Kinases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000251:Adenosine Triphosphatases