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

Biochem Biophys Res Commun. 2002 Dec 20;299(5):793-800. doi: 10.1016/s0006-291x(02)02718-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Microfilament Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Tensins
  • Receptor Protein-Tyrosine Kinases
  • axl receptor tyrosine kinase
  • TNS2 protein, human
  • Phosphoric Monoester Hydrolases

Associated data

  • GENBANK/AF518728
  • GENBANK/AF518729