KSR stimulates Raf-1 activity in a kinase-independent manner

被引:140
作者
Michaud, NR
Therrien, M
Cacace, A
Edsall, LC
Spiegel, S
Rubin, GM
Morrison, DK
机构
[1] GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007
[2] NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL BASIS CARCINOGENESIS LAB,FREDERICK,MD 21702
[3] UNIV CALIF BERKELEY,HOWARD HUGHES MED INST,DEPT MOL & CELL BIOL,BERKELEY,CA 94720
关键词
D O I
10.1073/pnas.94.24.12792
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras-dependent signaling pathways. Here, we find that murine KSR (mKSR1) translocates from the cytoplasm to the plasma membrane in the presence of activated Ras. At the membrane, mKSR1 modulates Ras signaling by enhancing Raf-1 activity in a kinase-independent manner, The activation of Raf-1 is mediated by the mKSR1 cysteine-rich CA3 domain and involves a detergent labile cofactor that is not ceramide, These findings reveal another point of regulation for Ras-mediated signal transduction and further define a noncatalytic role for mKSR1 in the multistep process of Raf-1 activation.
引用
收藏
页码:12792 / 12796
页数:5
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