The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl.
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.
Sekine
Yuichi
Y
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Yamamoto
Chikako
C
Ikeda
Osamu
O
Muromoto
Ryuta
R
Nanbo
Asuka
A
Oritani
Kenji
K
Yoshimura
Akihiko
A
Matsuda
Tadashi
T
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
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