The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl

Biochem Biophys Res Commun. 2009 Jun 26;384(2):187-92. doi: 10.1016/j.bbrc.2009.04.109. Epub 2009 May 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Neoplasm Proteins / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-cbl / genetics
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Ubiquitination

Substances

  • Adaptor Proteins, Signal Transducing
  • Neoplasm Proteins
  • Phosphoproteins
  • STAP2 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Proto-Oncogene Proteins c-cbl
  • Protein-Tyrosine Kinases
  • PTK6 protein, human
  • CBL protein, human