The insulin receptor kinase: modulation and therapeutic implications

Abstract

Following the binding of insulin to its cell surface receptor there is rapid activation of the insulin receptor kinase (IRK), leading to autophosphorylation of the receptor on tyrosine residues and the capacity to tyrosine phosphorylate various cellular substrates. The peroxovanadium compounds (pVs) were shown to activate the IRK in the complete absence of insulin and correlatively activate the full insulin signalling cascade. Along with earlier studies on mutant IRKs, this observation indicated that IRK function is both necessary and sufficient for insulin signaling. IRK is rapidly internalized into the endosomal apparatus (ENs), where it remains activated for a significant time and is capable of entraining insulin signalling events. Thus, modulation of the IRK in ENs is an important means by which insulin signalling is influenced. In recent years, several endosomal processes were shown to regulate IRK activity. The presence in ENs of a relatively specific insulin protease (endosomal acidic insulinase (E...