THE HUMAN MYT1 KINASE PREFERENTIALLY PHOSPHORYLATES CDC2 ON THREONINE-14 AND LOCALIZES TO THE ENDOPLASMIC-RETICULUM AND GOLGI-COMPLEX

Entry into mitosis requires the activity of the Cdc2 kinase. Cdc2 asso ciates with the B-type cyclins, and the Cdc2-cyclin B heterodimer is i n turn regulated by phosphorylation. Phosphorylation of threonine 161 is required for the Cdc2-cyclin B complex to be catalytically active, whereas phosphorylation of threonine 14 and tyrosine 15 is inhibitory. Human kinases that catalyze the phosphorylation of threonine 161 and tyrosine 15 have been identified. Here we report the isolation of a no vel human cDNA encoding a dual-specificity protein kinase (designated Myt1Hu) that preferentially phosphorylates Cdc2 on threonine 14 in a c yclin-dependent manner, Myt1Hu is 46% identical to Myt1Xe, a kinase re cently characterized from Xenopus laevis. Myt1Hu localizes to the endo plasmic reticulum and Golgi complex in HeLa cells. A stretch of hydrop hobic and uncharged amino acids located outside the catalytic domain O f Myt1Hu is the likely membrane-targeting domain, as its deletion resu lts in the localization of Myt1Hu primarily to the nucleus.