RGD Reference Report - Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein. - Rat Genome Database

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Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein.

Authors: Gout, I  Middleton, G  Adu, J  Ninkina, NN  Drobot, LB  Filonenko, V  Matsuka, G  Davies, AM  Waterfield, M  Buchman, VL 
Citation: Gout I, etal., EMBO J 2000 Aug 1;19(15):4015-25.
RGD ID: 727295
Pubmed: PMID:10921882   (View Abstract at PubMed)
PMCID: PMC306608   (View Article at PubMed Central)
DOI: DOI:10.1093/emboj/19.15.4015   (Journal Full-text)

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 p85 alpha 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 p110 alpha 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.

Objects referenced in this article
Gene Sh3kbp1 SH3 domain-containing kinase-binding protein 1 Rattus norvegicus

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