insulin signaling pathway
The binding of insulin to its receptor triggers a complex signaling cascade of protein phosphorylation and dephosphorylation culminating in the metabolic and mitogenic effects of insulin described above.
Elucidation of the insulin signaling pathway has been central to our understanding of the mechanisms underlying insulin resistance in diabetes.
The complete description of this intricate network is beyond the scope of this book,65 and we will only summarize some of the more pertinent mediators.
The insulin receptor is a tetrameric protein composed of two á- and two â-subunits. The â-subunit cytosolic domain possesses tyrosine kinase activity.
Insulin binding to the á-subunit extracellular domain activates the â-subunit tyrosine kinase, resulting in both autophosphorylation of the receptor and phosphorylation of downstream signal transduction elements.
For the sake of simplicity, we can separate the signaling pathways into two broad functional categories, mitogenic and metabolic, with the understanding that there may be considerable cross-talk between the protein intermediaries.
The mitogen-activated protein kinase (MAPK) pathway66 is responsible for the mitogenic effects of insulin (and insulin-like growth factors), promoting cellular proliferation and growth.
The metabolic effects of insulin are principally mediated by phosphatidylinositol-3-kinase (PI-3K).
References
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