Mitogen-activated protein kinase substrate specificity

Figure 11.2 Structure of the insulin receptor (a). Binding of insulin promotes autophosphorylation of the (3-subunits, where each (3-subunit phosphorylates the other (3-subunit. Phosphate groups are attached to three specific tyrosine residues (tyrosines 1158, 1162 and 1163), as indicated in (b). Activation of the (3-subunit s tyrosine kinase activity in turn results in the phosphorylation of various intracellular (protein) substrates which trigger the mitogen-activated protein kinase and/or the phosphoinositide (PI-3) kinase pathway responsible for inducing insulin s mitogenic and metabolic effects. The underlying molecular events occurring in these pathways are complex (e.g. refer to Combettes-Souverain, M. and Issad, T. 1998. Molecular basis of insulin action. Diabetes and Metabolism, 24, 477-489)...

The mitogenic activated protein kinase (MAPK) downstream from the Ras protein is organized in modules containing three types of protein kinases, which are successively activated by sequential phosphorylation events. The cell contains different MAPK modules, which differ in the nature of the triggering stimuli and the nature and specificity of the protein kinase components. The signal transducing function of a MAPK pathway is thus determined by the nature of the MAPK module involved this, in turn, depends on the properties of the protein kinases it contains, which differ in regulation and substrate specificity. The exact composition of the MAPK module is not fixed rather, different subtypes of protein kinase may be recruited to a module in a variable... 

C. Kinase Assay Using a Mitogen-Activated Protein Kinase-Specific Substrate... 

Stokoe D, Caudwell B, Cohen PT, Cohen P The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2. Biochem J 1993, 296(3) 843—849. 

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