Mitogen activated protein (MAP) kinase signal transduction pathways mediate the effects of various extracellular stimuli on biological processes such as proliferation, differentiation, and death. Three groups of mammalian MAP kinases have been identified: the extracellular signal-regulated kinases (ERK), the c-Jun N-terminal kinases (JNK), and the p38 MAP kinases. The p38 MAP kinases are activated by dual phosphorylation on Thr and Tyr within the motif Thr-Gly-Tyr located in kinase subdomain VIII. Activation of p38 MAPK is mediated specifically by the MAP kinase kinases MKK3 and MKK6, which are activated by a MAP kinase kinase kinase (MKKK). MKK3b, an alternatively spliced isoform of MKK3, contains an extra 29 N-terminal amino acids. Like MKK3 and MKK6, MKK3b specifically activates p38 MAPK and is more efficient than MKK3 in mediating downstream signaling events. Although MKK6 expression is limited, MKK3 and MKK3b are expressed in a wide range of cell types. MKK3, MKK3b, and MKK6 function as specific activators of p38 MAPK. However, they differ in their expression patterns and strength of kinase activity and, therefore, may differentially regulate p38 MAPK activation.
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2.Caution: Sodium azide yields highly toxic hydrazoic acid under acidic conditions. Dilute azide compounds in running water before discarding to avoid accumulation of potentially explosive deposits in plumbing.
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