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.
Hafizi
Sassan
S
Department of Clinical Chemistry, Lund University, Wallenberg Laboratory, University Hospital Malmö, SE-205 02 Malmö, Sweden.
Alindri
Filiz
F
Karlsson
Roger
R
Dahlbäck
Björn
B
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D017385:Sequence Homology; D000070876:Tensins; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques; D018909:src Homology Domains; D000094963:Axl Receptor Tyrosine Kinase
D008840:Microfilament Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D000070876:Tensins; D020794:Receptor Protein-Tyrosine Kinases; C452816:TNS2 protein, human; D010744:Phosphoric Monoester Hydrolases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human