MITOGEN-ACTIVATED PROTEIN-KINASE KINASE-1 (MKK1) IS NEGATIVELY REGULATED BY THREONINE PHOSPHORYLATION

Mitogen-activated protein kinase kinase 1 (MKK1), a dual-specificity t yrosine/threonine protein kinase, has been shown to be phosphorylated and activated by the raf oncogene product as part of the mitogen-activ ated protein kinase cascade. Here we report the phosphorylation and in activation of MKK1 by phosphorylation on threonine 286 and threonine 2 92. MKK1 contains a consensus phosphorylation site for p34(cdc2), a se rine/threonine protein kinase that regulates the cell division cycle, at Thr-286 and a related site at Thr-292. p34(cdc2) catalyzes the in v itro phosphorylation of MKK1 on both of these threonine residues and i nactivates MKK1 enzymatic activity. Both sites are phosphorylated in v ivo as well. The data presented in this report provide evidence that M KK1 is negatively regulated by threonine phosphorylation.