Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells

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• 作者：Barbara Nicke ; Julie Bastien ; Sophia J. Khanna ; Patricia H. Warne ; Victoria Cowling ; Simon J. Cook ; Gordon Peters ; Oona Delpuech ; Almut Schulze ; Katrien Berns et al.
• 刊名：Molecular Cell
• 出版年：2005
• 出版时间：9 December 2005
• 年：2005
• 卷：20
• 期：5
• 页码：673-685
• 全文大小：1663 K

文摘

Summary

The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21^WAF1/CIP1 has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kinome. Two known Ras-regulated kinases were identified, phosphoinositide 3-kinase p110α and ribosomal protein S6 kinase p70^S6K1, plus the MAP kinase kinase kinase kinase MINK, which had not previously been implicated in Ras signaling. MINK is activated after Ras induction via a mechanism involving reactive oxygen species and mediates stimulation of the stress-activated protein kinase p38 MAPK downstream of the Raf/ERK pathway. p38 MAPK activation is essential for Ras-induced p21^WAF1/CIP1 upregulation and cell cycle arrest. MINK is thus a distal target of Ras signaling in the induction of a growth-arrested, senescent-like phenotype that may act to oppose oncogenic transformation in HOSE cells.