IDENTIFICATION OF A DUAL-SPECIFICITY KINASE THAT ACTIVATES THE JUN KINASES AND P38-MPK2

One Ras-dependent protein kinase cascade leading from growth factor re ceptors to the ERK (extracellular signal-regulated kinases) subgroup o f mitogen-activated protein kinases (MAPKs) is dependent on the protei n kinase Raf-1, which activates the MEK(MAPK or ERK kinase) dual speci ficity kinases. A second protein kinase cascade leading to activation of the Jun kinases (JNKs) is dependent on MEKK (MEK kinase). A dual-sp ecificity kinase that activates JNK, named JNKK, was identified that f unctions between MEKK and JNK. JNKK activated the JNKs but did not act ivate the ERKs and was unresponsive to Raf-1 in transfected Hela cells . JNKK also activated another MAPK, p38 (Mpk2; the mammalian homolog o f HOG1 from yeast), whose activity is regulated similarly to that of t he JNKs.