NETWORKING WITH MITOGEN-ACTIVATED PROTEIN-KINASES

Mitogen activated protein (MAP) kinases and their target ribosomal pro tein S6 (RSK) kinases have been recognized as shared components in the intracellular signaling pathways of many diverse cytokines. Recent st udies have extended this protein kinase cascade by identifying the maj or activator of vertebrate MAP kinases as a serine/threonine/tyrosine- protein kinase called MEK, which is related to yeast mating factor-reg ulated protein kinases encoded by the STE7 and byr1 genes. MEK, in tur n, may be activated following its phosphorylation on serine by either of the kinases encoded by proto-oncogenes raf1 or mos, as well as by p 78(mekk), which is related to the yeast STE11 and byr2 gene products. Isoforms of ah of these protein kinases may specifically combine to as semble distinct modules for intracellular signal transmission. However , the fundamental architecture of these protein kinase cascades has be en highly conserved during eukaryotic evolution.