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Molecular mechanisms regulating the hyaluronan binding activity of the adhesion protein CD44

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Summary

In the present study, we describe the isolation and characterization of a cDNA clone designated B6F1.3, that appears to ‘activate’ the hyaluronan-binding capacity of CD44 upon transfection into the murine fibroblastoid cell line MOP8. Sequence analysis indicates that the putative regulatory molecule encoded by this clone is identical to the murine interleukin-2 receptor γ chain (mIL-2Rγ), a recently described type 1 transmembrane protein that constitutes an integral component of the cell surface receptors that bind a number of cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and perhaps also IL-13. Mutations in this molecule have been shown to be responsible for X-linked severe combined immunodeficiency (XSCID) in humans. With the exception of bone marrow, the mIL-2Rγ chain was found to be expressed at high levels on all hemopoietic cell lines and tissue types examined. Non-hemopoietic tissues are generally negative. FACS analysis and Western blot analysis indicated respectively that B6F1.3 does not mediate its effects by upregulating the expression of CD44 or by altering the alternative splicing of the molecule. Removal of the cytoplasmic tail of the mIL-2Rγ chain, including a Src homology region 2 (SH2) subdomain, abolished its ability to enhance CD44-mediated binding to hyaluronan suggesting the involvement of signal transduction events triggered via the cytoplasmic domain in the ‘activation’ process. Determining whether activating molecules such as B6F1.3 are co-expressed within tumor cells may help improve the potential value of CD44 as a diagnostic marker of metastatic disease.

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Authors and Affiliations

  1. Terry Fox Laboratory, B.C. Cancer Agency, 601 West 10th. Avenue, V5Z 1L3, Vancouver, British Columbia, Canada

    Roland K. Chiu, Armin Droll, Julie F. Dirks & Graeme J. Dougherty

  2. Department of Radiation Oncology, B.C. Cancer Agency, 601 West 10th. Avenue, V5Z 1L3, Vancouver, British Columbia, Canada

    Shona T. Dougherty

  3. Department of Pathology, University of Pittsburgh, 15261, Pittsburgh, PA, USA

    David L. Cooper

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  1. Roland K. Chiu
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  2. Armin Droll
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  4. Shona T. Dougherty
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  5. Julie F. Dirks
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  6. Graeme J. Dougherty
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Chiu, R.K., Droll, A., Cooper, D.L. et al. Molecular mechanisms regulating the hyaluronan binding activity of the adhesion protein CD44. J Neuro-Oncol 26, 231–239 (1995). https://doi.org/10.1007/BF01052626

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