title: The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl.
abstract: Signal transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2 (SH2)-like domains as well as a YXXQ motif in its C-terminal region. Our previous study in T cells demonstrated that STAP-2 influences FAK protein levels through recruitment of E3 ubiquitin ligase, Cbl, to FAK. In the present study, we found that Cbl directly controls the protein levels and activity of STAP-2. STAP-2 physically interacted with Cbl through its PH and SH2-like domains. Small-interfering RNA-mediated reduction of endogenous Cbl restored STAP-2 protein levels. In contrast, over-expression of Cbl induced STAP-2 degradation. Importantly, Cbl-mediated regulation of STAP-2 protein levels affected Brk/STAP-2-induced STAT3 activation. These results indicate that Cbl regulates STAP-2 protein levels and Brk/STAP-2-mediated STAT3 activation.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Chikako
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Ikeda
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Asuka
authors.initials: A
authors.lastname: Nanbo
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009363:Neoplasm Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; D010750:Phosphoproteins; C413897:STAP2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050721:Proto-Oncogene Proteins c-cbl; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human; C067419:CBL protein, human