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Negative regulation of PI 3‐kinase by Ruk, a novel adaptor protein
Author(s) -
Gout Ivan,
Middleton Gayle,
Adu Jimi,
Ninkitalia N.,
Drobot Ludmila B.,
Filonenko Valery,
Matsuka Gennady,
Davies Alun M.,
Waterfield Michael,
Buchman Vladimir L.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.15.4015
Subject(s) - library science , classics , art history , art , computer science
Class I A phosphatidylinositol 3‐kinase (PI 3‐kinase) is a key component of important intracellular signalling cascades. We have identified an adaptor protein, Ruk l , which forms complexes with the PI 3‐kinase holoenzyme in vitro and in vivo . This interaction involves the proline‐rich region of Ruk and the SH3 domain of the p85α regulatory subunit of the class I A PI 3‐kinase. In contrast to many other adaptor proteins that activate PI 3‐kinase, interaction with Ruk l substantially inhibits the lipid kinase activity of the enzyme. Overexpression of Ruk l in cultured primary neurons induces apoptosis, an effect that could be reversed by co‐expression of constitutively activated forms of the p110α catalytic subunit of PI 3‐kinase or its downstream effector PKB/Akt. Our data provide evidence for the existence of a negative regulator of the PI 3‐kinase signalling pathway that is essential for maintaining cellular homeostasis. Structural similarities between Ruk, CIN85 and CD2AP/CMS suggest that these proteins form a novel family of adaptor molecules that are involved in various intracellular signalling pathways.