The 96 kDa protein kinase activated by oncogenic Ras in Xenopus egg extracts is also activated by constitutively active Mek: activation requires serine/threonine phosphorylation.
In the Xenopus egg and oocyte system, oncogenic Ras protein can induce cell cycle arrest. The effect of oncogenic Ras on the cell cycle seems to be mediated by the Raf-Mek-Erk pathway of Ras signal transduction since constitutively active Raf, Mek, or Erk can mimic the effect of oncogenic Ras protein and since specific inhibition of these kinases can block the effect of oncogenic Ras. Using activated Xenopus egg extracts, we previously reported that the cell cycle arrest induced by oncogenic Ras correlates with the activation of a 96 kDa protein that phosphorylates histone h2b in vitro. This result raised the possibility that the 96 kDa kinase (designated as p96h2bk) is a potential target of the Raf-Mek-Erk pathway that links the pathway to the control of the cell cycle. We report here that constitutively active Mek1 could activate p96h2bk in the absence of oncogenic Ras. Moreover, inhibition of endogenous Mek by a specific inhibitor, PD 098059, suppressed the activation of p96h2bk by oncogenic Ras. These results are consistent with the concept that p96h2bk is a component or target of the Raf-Mek-Erk pathway. Furthermore, we have shown that activation of p96h2bk requires serine/threonine phosphorylation of p96h2bk.
Pan
B T
BT
Department of Surgery, University of Kentucky Chandler Medical Center, Lexington 40536, USA.
Zhang
Y
Y
Brott
B
B
Chen
D H
DH
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002453:Cell Cycle; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D048369:MAP Kinase Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D019319:Okadaic Acid / Q000494:pharmacology; D009865:Oocytes; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D006656:Protamine Kinase / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D014982:Xenopus laevis; D019061:src-Family Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D006657:Histones; D010769:Phosphothreonine; D010768:Phosphoserine; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D006656:Protamine Kinase; D017346:Protein Serine-Threonine Kinases; C105680:histone h2b kinase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D016283:Proto-Oncogene Proteins p21(ras); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one