FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade (Articolo in rivista)

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  • FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/ncb2731 (literal)
Alternative label
  • Kuchay Shafi1,2; Duan Shanshan1; Schenkein Emily1; Peschiaroli Angelo1*; Saraf Anita2,3; Florens Laurence2,3; Washburn Michael P.2,3,4; Pagano Michele1,2 (2013)
    FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade
    in Nature cell biology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Kuchay Shafi1,2; Duan Shanshan1; Schenkein Emily1; Peschiaroli Angelo1*; Saraf Anita2,3; Florens Laurence2,3; Washburn Michael P.2,3,4; Pagano Michele1,2 (literal)
Pagina inizio
  • 472 (literal)
Pagina fine
  • 480 (literal)
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  • Epub 2013 Apr 21 (literal)
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  • 15 (literal)
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  • 5 (literal)
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  • 1 Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, New York 10016, USA. 2 Howard Hughes Medical Institute, USA. 3 The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA. 4 Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA. *Present address: Centro Nazionale Ricerche, Institute of Cellular Biology and Neurobiology, Via E. Ramarini 32, 00015, Rome, Italy. (literal)
Titolo
  • FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory subunit controls the PI(3)K signalling cascade (literal)
Abstract
  • F-box proteins are the substrate-recognition subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes. Purification of the F-box protein FBXL2 identified the PI(3)K regulatory subunit p85beta and tyrosine phosphatase PTPL1 as interacting proteins. FBXL2 interacts with the pool of p85beta that is free of p110 PI(3)K catalytic subunits and targets this pool for ubiquitylation and subsequent proteasomal degradation. FBXL2-mediated degradation of p85beta is dependent on the integrity of its CaaX motif. Whereas most SCF substrates require phosphorylation to interact with their F-box proteins, phosphorylation of p85beta on Tyr 655, which is adjacent to the degron, inhibits p85beta binding to FBXL2. Dephosphorylation of phospho-Tyr-655 by PTPL1 stimulates p85beta binding to and degradation through FBXL2. Finally, defects in the FBXL2-mediated degradation of p85beta inhibit the binding of p110 subunits to IRS1, attenuate the PI(3)K signalling cascade and promote autophagy. We propose that FBXL2 and PTPL1 suppress p85beta levels, preventing the inhibition of PI(3)K by an excess of free p85 that could compete with p85-p110 heterodimers for IRS1. (literal)
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