The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation

FEBS Lett. 1997 Sep 22;415(1):59-63. doi: 10.1016/s0014-5793(97)01093-4.

Abstract

The product of gas6 (Gas6) is a growth factor with high level of similarity to protein S and was identified as the ligand for Axl family of tyrosine kinase receptors. Gas6 contains an N-terminal gamma-carboxylated domain (Gla), four epidermal growth factor like domains and a large C-terminal D region. An alternative Gas6 spliced form (Gas6SV) having an additional 43 amino acids between fourth EFG like and D domain was characterised. Here we show data indicating that Gas6SV is specifically cleaved within the inserted sequence, thereby splitting the D domain from the remaining part of the protein. The resulting two proteolytic products of 36 kDa and 50 kDa were separated and the 50 kDa fragment corresponding to region D was shown to be responsible for Axl receptor activation. Furthermore a deletion mutant of Gas6 containing only the D domain was shown to similarly activate Axl receptor phosphorylation unequivocally demonstrating that D domain can act as a signalling molecule. The possible roles of the proteolytic processing of Gas6SV in the regulation of growth factor availability are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Axl Receptor Tyrosine Kinase
  • Blotting, Western
  • COS Cells
  • Cell Line
  • DNA Mutational Analysis
  • Enzyme Activation
  • Epidermal Growth Factor / chemistry
  • Gene Expression Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Protein Processing, Post-Translational
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism*
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Sequence Deletion
  • Transfection

Substances

  • Intercellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • growth arrest-specific protein 6
  • Epidermal Growth Factor
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human