A dominant-negative mutant of raf blocks mitogen-activated protein kinase activation by growth factors and oncogenic p21ras.
作者： D Schaap , J van der Wal , L.R. Howe , C.J. Marshall , W.J. van Blitterswijk
DOI: 10.1016/S0021-9258(20)80719-4
关键词: c-Raf 、 Cyclin-dependent kinase 9 、 Protein kinase C 、 MAP kinase kinase kinase 、 MAP2K7 、 Mitogen-activated protein kinase kinase 、 ASK1 、 Cell biology 、 MAP kinase kinase activity 、 Biology 、 Biochemistry
摘要: p74raf-1, a serine/threonine kinase, is structurally related to the protein kinase C (PKC) family and contains cysteine motif in its N-terminal domain, which essential for regulation. It has been shown that p74raf-1 functions upstream of mitogen-activated (MAP) kinase. We have constructed mutant (N delta raf) only regulatory domain. When transiently expressed COS-M6 cells, N raf efficiently blocked activation MAP extracellular signal regulated (ERK2), induced by either epidermal growth factor, phorbol ester, serum, or oncogenic p21ras. Similar constructs with motifs from PKC-alpha diacylglycerol did not inhibit ERK2. Overexpression full-length rescued inhibition ERK2 stimulus dependent manner, indicating acts as competitive inhibitor wild-type p74raf-1. In contrast, overexpression PKC-alpha, -epsilon, -zeta raf-containing cells could rescue conclude an mediator factor- ester-induced activity cannot be substituted -epsilon -zeta.
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