Regulation of Raf-1 by Direct Feedback Phosphorylation
نویسندگان
چکیده
منابع مشابه
Regulation of Raf-1 by direct feedback phosphorylation.
The Raf-1 kinase is an important signaling molecule, functioning in the Ras pathway to transmit mitogenic, differentiative, and oncogenic signals to the downstream kinases MEK and ERK. Because of its integral role in cell signaling, Raf-1 activity must be precisely controlled. Previous studies have shown that phosphorylation is required for Raf-1 activation, and here, we identify six phosphoryl...
متن کاملNegative regulation of Raf-1 by phosphorylation of serine 621.
The elevation of cyclic AMP (cAMP) levels in the cell downregulates the activity of the Raf-1 kinase. It has been suggested that this effect is due to the activation of cAMP-dependent protein kinase (PKA), which can directly phosphorylate Raf-1 in vitro. In this study, we confirmed this hypothesis by coexpressing Raf-1 with the constitutively active catalytic subunit of PKA, which could fully r...
متن کاملRegulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association.
The Raf-1 kinase domain is kept in an inactive state by the N-terminal regulatory domain. Activation of the kinase domain occurs following release from the N-terminal repression and possible catalytic upregulation. To distinguish the regulatory mechanisms that directly influence the catalytic activity of the enzyme from those which act through the inhibitory domain, the catalytic domain of Raf-...
متن کاملInteraction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1.
Activation of Raf-1 is a complex process in which phosphorylation of Ser(338)-Tyr(341) is a critical step. Previous studies have shown that Pak1/2 is implicated in both Ras-dependent and -independent activation of Raf-1 by phosphorylating Raf Ser(338). The present study explores the structural basis of Raf-1 phosphorylation by Pak1. We found that Pak directly associates with Raf-1 under both ph...
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Oscillating cyclin-dependent kinase 1 (Cdk1) activity is the major regulator of cell-cycle progression, whereas the Aurora B kinase, as part of the chromosome passenger complex (CPC), controls critical aspects of mitosis such as chromosome condensation and biorientation on the spindle. How these kinases mechanistically coordinate their important functions is only partially understood. Here, usi...
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ژورنال
عنوان ژورنال: Molecular Cell
سال: 2005
ISSN: 1097-2765
DOI: 10.1016/j.molcel.2004.11.055