P38 group of MAP kinases, one of the four main sub-groups, serve as a nexus for signal transduction and play a vital role in numerous biological processes. For example, mammalian p38s show the roles and activation has been shown to occur in response to extracellular stimuli such as UV light, heat, osmotic shock, inflammatory cytokines (TNF-α & IL-1), and growth factors (CSF-1). In upstream kinases, there are two main MAPKKs that are known to activate p38, which are respectively MKK3 and MKK6. It is proposed that upstream kinases can differentially regulate p38 isoforms as evidenced by the inability of MKK3 to effectively activate p38β while MKK6 is a potent activator despite 80% homology between these two MKKs. This also suggests that activation of p38 isoforms can be specifically controlled through different regulators and coactivated by various combinations of upstream regulators. in downregulation of the p38, dephosphorylation plays a major role.

p38 MAPK Signaling Pathway References