Expression of splice variants of the human ADAM15 gene and strong interaction between the cytoplasmic domain of one variant and Src family proteins Lck and Hck

Pathobiology. 2004;71(4):185-92. doi: 10.1159/000078672.

Abstract

Objective: The aim of the present study was to show variant species of ADAM15 and unique Src homology 3 (SH3)-binding motifs, which strongly bound Src family proteins compared with ADAM15.

Methods and results: RT-PCR using primers for the cytoplasmic domain revealed the presence of different species, designated ADAM15v1 and ADAM15v2, which had characteristic SH3-binding class I and class II motifs. The mRNA of ADAM15v1 and ADAM15v2 was mainly found in peripheral blood mononuclear cells, T lymphocytes and monocytic cell lines. ADAM15v2 protein interacted more strongly with the Src family proteins Lck and Hck than did ADAM15 protein, as examined by pull-down analysis and immunoprecipitation followed by immunoblot analysis. The binding with Lck and Hck was enhanced by the phosphorylation of ADAM15v2 protein.

Conclusions: These results suggest that the cytoplasmic domain of ADAM15v2 strongly interacts with Lck and Hck and regulates leukocyte function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • Alternative Splicing*
  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • DNA, Recombinant*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics*
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Membrane Proteins / classification
  • Membrane Proteins / genetics*
  • Metalloendopeptidases / classification
  • Metalloendopeptidases / genetics*
  • Molecular Sequence Data
  • Protein Structure, Tertiary / genetics
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-hck
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA, Recombinant
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • HCK protein, human
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins c-hck
  • ADAM Proteins
  • ADAM15 protein, human
  • Metalloendopeptidases