Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif.

Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Research Abstract Details 

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Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Abstract Text:

Marielle E Yohe,Kent L Rossman,Olivia S Gardner,Antoine E Karnoub,Jason T Snyder,Svetlana Gershburg,Lee M Graves,Channing J Der,John Sondek,

Dbl-related oncoproteins are guanine nucleotide exchange factors specific for Rho-family GTPases and typically possess tandem Dbl homology (DH) and pleckstrin homology domains that act in concert to catalyze exchange. Because the ability of many Dbl-family proteins to catalyze exchange is constitutively activated by truncations N-terminal to their DH domains, it has been proposed that the activity of Dbl-family proteins is regulated by auto-inhibition. However, the exact mechanisms of regulation of Dbl-family proteins remain poorly understood. Here we show that the Dbl-family protein, Tim, is auto-inhibited by a short, helical motif immediately N-terminal to its DH domain, which directly occludes the catalytic surface of the DH domain to prevent GTPase activation. Similar to the distantly related Vav isozymes, auto-inhibition of Tim is relieved by truncation, mutation, or phosphorylation of the auto-inhibitory helix. A peptide comprising the helical motif inhibits the exchange activity of Tim in vitro. Furthermore, substitutions within the most highly conserved surface of the DH domain designed to disrupt interactions with the auto-inhibitory helix also activate the exchange process.

Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Publishing Authors By Initials

ME Yohe,KL Rossman,OS Gardner,AE Karnoub,JT Snyder,S Gershburg,LM Graves,CJ Der,J Sondek,

For similar proteins: recombinant proteins research abstracts see: proteins: recombinant proteins research

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Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 13813-23

Journal Abbreviation:

ISSN: 0021-9258

DAY: 2

MONTH: 03

YEAR: 2007

Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Keywords Mesh Terms:

KEYWORDS: Recombinant Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif. Information

Substance Name: Timeless protein, mouse

Registry Number: 0

Grant and Affiliation Information for Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif.

AFFILIATION: Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM65533

ACRONYM: GM

MEDLINETA: J Biol Chem

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