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.
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.


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.
Yasui
Atsushi
A
Department of Immunology and Allergy, Oita Medical University, Oita, Japan.
Matsuura
Keiko
K
Shimizu
Eiichi
E
Hijiya
Naoki
N
Higuchi
Yasunori
Y
Yamamoto
Shunsuke
S
D051722:ADAM Proteins; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004274:DNA, Recombinant; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics*; D008666:Metalloendopeptidases / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004274:DNA, Recombinant; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051572:Proto-Oncogene Proteins c-hck; D051722:ADAM Proteins; C098660:ADAM15 protein, human; D008666:Metalloendopeptidases