Activation of p38 alpha/beta MAPK

p38 alpha/beta MAPK is well established as a promyogenic kinase, but the mechanism by which it is activated during differentiation is not well understood. CDO, JLP and p38 form a ternary complex and it is anticipated that in its role as a scaffold, JLP brings additional components of the pathway, such as MKKs, to these complexes and cooperate to activate p38 alpha/beta MAPK pathway. p38 is activated by phosphorylation on a canonical TxY motif by dual specificity kinases MKK6 and MKK3. MKK6 is the most abundant in skeletal muscles and displays minimal substrate selectivity among all p38 isoforms.

p38α/β MAPK 作为一种促进细胞分化的激酶已被广泛认可，然而其在分化过程中被激活的机制尚不明确。CDO、JLP 和 p38 共同构成一个三元复合体，预计在此结构支架的作用下，JLP 将途径中的额外成分，如 MKKs 等引入这些复合体，并与它们协同作用以激活 p38α/β MAPK 途径。p38 通过在经典 TxY 模式上被双特异性激酶 MKK6 和 MKK3 磷酸化而被激活。MKK6 在骨骼肌中含量最为丰富，且在所有 p38 亚型中显示出最小的底物选择性。