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Meltrin α cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src

Oncogene volume 19, pages 5842–5850 (2000)Cite this article

Abstract

Meltrin α/ADAM12 is a member of the ADAM/MDC family proteins characterized by the presence of metalloprotease and disintegrin domains. This protein also contains a single transmembrane domain and a relatively long cytoplasmic domain containing several proline-rich sequences. These sequences are compatible with the consensus sequences for binding the Src homology 3 (SH3) domains. To determine whether the proline-rich sequences interact with SH3 domains in several proteins, binding of recombinant SH3 domains to the meltrin α cytoplasmic domain was analysed by pull-down assays. The SH3 domains of Src and Yes bound strongly, but that of Abl or phosphatidylinositol 3-kinase p85 subunit did not. Full-length Grb2/Ash bound strongly, whereas its N-terminal SH3 domain alone did less strongly. Src and Grb2 in bovine brain extracts also bound to meltrin α cytoplasmic domain on affinity resin. Furthermore, immunoprecipitation with a monoclonal antibody to meltrin α resulted in coprecipitation of Src and Grb2 with meltrin α in cell extracts, suggesting that Src and Grb2 are associated in vivo with meltrin α cytoplasmic domain. This notion was also supported by the findings that exogenously expressed meltrin α cytoplasmic domain coexisted with Src and Grb2 on the membrane ruffles. The C-terminal Tyr901 of meltrin α was phosphorylated both in vitro and in cultured cells by v-Src. These results may imply that meltrin α cytoplasmic domain is involved in a signal transduction for some biological function through the interaction with SH3-containing proteins.

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Acknowledgements

We are grateful to Dr Marius Sudol for the generous gift of the SH3 domain cDNA collections and to Drs Michinari Hamaguchi and Hidesaburo Hanafusa for pSR-XD2. C3H/10T1/2 cells were obtained from Japanese Cancer Research Resources Bank (JCRB). This study was partly supported by research grants from the Ministry of Education, Science, Sports, and Culture of Japan and from the Ministry of Health and Welfare of Japan for Nervous and Mental Disorders (8A-1 and 11B-1).

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  1. Department of Biology, Faculty of Science, Chiba University, Yayoicho, Inageku, Chiba, Chiba, 263-8522, Japan

    Akiko Suzuki, Nae Kadota, Tomokazu Hara, Yoshiko Nakagami, Toshiaki Izumi & Takeshi Endo

  2. Department of Biochemistry, Institute of Medical Science, University of Tokyo, Shirokanedai, Minatoku, 108-8639, Tokyo, Japan

    Tadaomi Takenawa

  3. Department of Molecular Biology, Osaka Bioscience Institute, Suita, 565-0874, Osaka, Japan

    Hisataka Sabe

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  1. Akiko Suzuki
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Suzuki, A., Kadota, N., Hara, T. et al. Meltrin α cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src. Oncogene 19, 5842–5850 (2000). https://doi.org/10.1038/sj.onc.1203986

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