IGF Regulation of Apoptosis

Model of IGF-I Receptor regulation of apoptosis. Ligand binding to IGF-IR activates the tyrosine kinase domain which initiates a set of signaling cascades. This leads to a higher concentration of the anti-apoptotic proteins bcl-2 and bcl-x_L a lower level of the apoptotic proteins bax and bcl-x_s. IGF-IR signaling also activates phosphatidylinositol 3-kinase (P13-K), which in turn activates protein kinase B (PKB/Akt) that also prevent apoptosis. These pathways converge on the inhibition of caspases, especially caspase-3, which is then blocked from performing an apoptosis-initiating cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) and blocked from degrading β-catenin, part of the cadherin cell-adhesion system. Thus, IGF stimulates IGF-IR to lower the probability of apoptosis initiation and to retain cell-to-cell junctions.

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