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Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin.

Axl receptor tyrosine kinase is implicated in several malignancies and is the receptor for the vitamin K-dependent growth factor Gas6. From a yeast two-hybrid screen of protein-protein interactions with the Axl cytoplasmic domain, we detected a previously uncharacterised SH2 domain-containing protein. We cloned two novel splice variants of this protein that give rise to 1409- and 1419-amino acid proteins, differing only in their N-terminal residues and yielding a 150-kDa protein product by in vitro translation. The Axl-interacting C-terminus contains a tandem SH2 and PTB domain combination homologous to the focal adhesion protein tensin. We detected interaction of Axl with both domains in mammalian cells by co-immunoprecipitation and two-hybrid analyses. In addition, the protein possesses an N-terminal putative phorbol ester-binding C1 domain as well as a central tyrosine phosphatase motif. Thus, we have named the protein C1 domain-containing phosphatase and TENsin homologue (C1-TEN). Northern blot analysis of C1-TEN in human tissues revealed highest expression in heart, kidney, and liver. In summary, we have identified a novel multi-domain intracellular protein that interacts with Axl and which may furthermore be involved in other signal transduction pathways.

Pubmed ID: 12470648


  • Hafizi S
  • Alindri F
  • Karlsson R
  • Dahlb├Ąck B


Biochemical and biophysical research communications

Publication Data

December 20, 2002

Associated Grants


Mesh Terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Cloning, Molecular
  • Humans
  • Microfilament Proteins
  • Molecular Sequence Data
  • Oncogene Proteins
  • Phosphoric Monoester Hydrolases
  • Precipitin Tests
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Sequence Homology
  • Tissue Distribution
  • Two-Hybrid System Techniques
  • src Homology Domains