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.
journal_name
Proc Natl Acad Sci U S Aauthors
Cutler RE Jr,Stephens RM,Saracino MR,Morrison DKdoi
10.1073/pnas.95.16.9214subject
Has Abstractpub_date
1998-08-04 00:00:00pages
9214-9issue
16eissn
0027-8424issn
1091-6490journal_volume
95pub_type
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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