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XB-ART-14499
Proc Natl Acad Sci U S A 1998 Aug 04;9516:9214-9. doi: 10.1073/pnas.95.16.9214.
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Autoregulation of the Raf-1 serine/threonine kinase.

Cutler RE , Stephens RM , Saracino MR , Morrison DK .


Abstract
The Raf-1 serine/threonine kinase is a key protein involved in the transmission of many growth and developmental signals. In this report, we show that autoinhibition mediated by the noncatalytic, N-terminal regulatory region of Raf-1 is an important mechanism regulating Raf-1 function. The inhibition of the regulatory region occurs, at least in part, through binding interactions involving the cysteine-rich domain. Events that disrupt this autoinhibition, such as mutation of the cysteine-rich domain or a mutation mimicking an activating phosphorylation event (Y340D), alleviate the repression of the regulatory region and increase Raf-1 activity. Based on the striking similarites between the autoregulation of the serine/threonine kinases protein kinase C, Byr2, and Raf-1, we propose that relief of autorepression and activation at the plasma membrane is an evolutionarily conserved mechanism of kinase regulation.

PubMed ID: 9689060
PMC ID: PMC21318
Article link: Proc Natl Acad Sci U S A


Species referenced: Xenopus laevis
Genes referenced: raf1

References [+] :
Beck, The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus. 1987, Pubmed