CD30 Ligand Signal Transduction Involves Activation of a Tyrosine Kinase and of Mitogen-activated Protein Kinase in a Hodgkin's Lymphoma Cell Line

Clemens Martin Wendtner, Barbara Schmitt, Bertold Emmerich, Michael Hallek, Brian J. Druker, Hans Jürgen Gruss, Raymond G. Goodwin

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

CD30 is a transmembrane receptor of the nerve growth factor/tumor necrosis factor receptor superfamily. Its expression is associated with Hodgkin's lymphoma and a subset of non-Hodgkin's lymphoma. Recently, its ligand (CD30L) has been cloned. CD30L enhances the proliferation of peripheral T cells and the Hodgkin's cell line HDLM-2 but seems to exert antiproliferative effects on large cell anaplastic lymphoma cell lines. Since tyrosine kinases are critical regulators of cell growth, we investigated whether CD30L induced changes in cellular tyrosine phosphorylation in CD30-positive lymphoma cell lines. Stimulation with CD30L or with an agonistic mAb against CD30, M44, induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of a cytosolic protein of Mr 42,000 (p42) in the Hodgkin's lymphoma cell line HDLM-2 but not in other CD30-positive lymphomas. In HDLM-2 cells, the phorbol ester phorbol 12-myristate 13-acetate also stimulated tyrosine phosphorylation of p42, and this effect was enhanced by M44. In marked contrast, agents stimulating the protein kinase A pathway, like forskolin or dibutyryl cAMP, did not affect tyrosine phosphorylation of p42. By immunoprecipitation with mAbs against mitogen-activated protein kinase (MAPK; p42ERK11), a Mr 42,000 protein was identified which comigrated with p42 on SDS gels and which was phosphorylated on tyrosine residues in response to stimulation of CD30. Immune complex kinase assays showed that M44 mAb induced the activation of MAPK (p42ERKM) and the phosphorylation of a MAPK substrate, myelin basic protein. Taken together, the results suggest that CD30L induces the tyrosine phosphorylation and activation of the MAPK p42ERKii isoform in HDLM-2 cells. These findings may have implications for the understanding of the pathogenesis of Hodgkin's disease.

Original languageEnglish (US)
Pages (from-to)4157-4161
Number of pages5
JournalCancer Research
Volume55
Issue number18
StatePublished - Sep 15 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wendtner, C. M., Schmitt, B., Emmerich, B., Hallek, M., Druker, B. J., Gruss, H. J., & Goodwin, R. G. (1995). CD30 Ligand Signal Transduction Involves Activation of a Tyrosine Kinase and of Mitogen-activated Protein Kinase in a Hodgkin's Lymphoma Cell Line. Cancer Research, 55(18), 4157-4161.