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Cloning and characterization of human Src-like adaptor protein 2 and a novel splice isoform, SLAP-2-v

Oncogene volume 22, pages 266–273 (2003)Cite this article

Abstract

Src-like adaptor protein 2 (SLAP-2) is a recently characterized adaptor protein bearing sequence and structural similarity to the Src-like adaptor protein (SLAP). SLAP-2 expression is hematopoietic-specific, and it has been demonstrated to function as a negative regulator of T-cell antigen receptor (TCR)-mediated signalling by virtue of its interaction with c-Cbl. Here we report the cloning of a cDNA encoding the human homologue of SLAP-2, as well as the genomic structure of the human SLAP-2 gene. Similar to its murine counterpart, two human SLAP-2 protein isoforms exist because of alternative translation initiation, and SLAP-2 protein expression is observed in a variety of hematopoietic cell lines of both lymphoid and myeloid lineages. The human SLAP-2 gene is located on chromosome 20q, and the SLAP-2 coding region consists of seven exons. Concurrent with the cloning of the full-length SLAP-2 cDNA, a unique cDNA encoding an alternatively spliced SLAP-2 isoform has been identified, and designated as SLAP-2-v. The SLAP-2-v transcript encodes a putative protein of 210 amino acids that lacks the c-Cbl interaction region, and consequently is impaired in its ability to both bind to c-Cbl, and inhibit TCR signalling relative to SLAP-2.

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Acknowledgements

We thank Derek Bouman and Kathy Chun for the FISH analysis, and Hamid Band and Morag Park for the Cbl-N GST fusion construct. As well, we thank Donna Berry and Dwayne Barber for comments on the manuscript. Michael P Loreto is a recipient of a scholarship from the Natural Science and Engineering Research Council of Canada (NSERC). C Jane McGlade is a research scientist of the National Cancer Institute of Canada (NCIC). This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Leukemia Research Fund of Canada (LRF).

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  1. Department of Medical Biophysics, University of Toronto, Canada

    Michael P Loreto & C Jane McGlade

  2. The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, M5G1X8, Ontario, Canada

    Michael P Loreto & C Jane McGlade

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  1. Michael P Loreto
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Correspondence to C Jane McGlade.

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Loreto, M., McGlade, C. Cloning and characterization of human Src-like adaptor protein 2 and a novel splice isoform, SLAP-2-v. Oncogene 22, 266–273 (2003). https://doi.org/10.1038/sj.onc.1206114

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