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Substrates and signalling complexes: the tortured path to insulin action
1Department of Pharmacology, Stanford University School of Medicine, California 94305.
Abstract:
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.
Insights
Identifying substrates of insulin receptor tyrosine kinase is crucial for understanding insulin signaling. However, their exact roles in insulin
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- Insulin receptor tyrosine kinase (IRTK) plays a key role in insulin signaling.
- Several proteins have been identified as potential substrates of IRLK.
- The precise biological functions of these substrates remain largely unknown.
Purpose of the Study:
- To review the identified substrates of IRLK.
- To discuss the potential roles of these substrates in insulin signaling pathways.
- To explore the mechanisms of insulin signal transduction.
Main Methods:
- Literature review of studies on IRLK substrates.
- Analysis of data on protein identification and characterization.
- Discussion of signaling complex formation versus direct substrate phosphorylation.
Main Results:
- Several potential IRLK substrates have been identified, including pp15, pp120, pp42, pp85, and pp185.
- Tyrosine phosphorylation of some substrates correlates with receptor signaling.
- Recent findings suggest pp42 phosphorylation may be due to autophosphorylation, not IRLK.
Conclusions:
- The exact roles of IRLK substrates in mediating insulin's biological responses are still undetermined.
- The mechanism of insulin signaling may involve substrate phosphorylation or signaling complex formation.
- Further research is needed to elucidate the precise functions of IRLK substrates.