Inhibition of protein tyrosine kinases or protein kinase C prevents nonspecific killer T lymphocyte-mediated tumoricidal activity

B. Hope Stewart, David W. Hoskin

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The signal transduction events which govern major histocompatibility complex-unrestricted tumour cell destruction by nonspecific killer T lymphocytes induced with anti-CD3 antibody have not yet been determined. In this study we used pharmacologic inhibitors to investigate the role of protein tyrosine kinases (PTK) and protein kinase C (PKC) in this process. The PTK-inhibitors herbimycin A, genistein, and methyl 2,5-dihydroxycinnamate blocked anti-CD3-activated killer T (AK-T) lymphocyte-mediated killing of tumour target cells. The PKC-inhibitors staurosporine, calphostin C, and myristoylated PKC pseudosubstrate peptide, as well as PKC desensitization by phorbol 12-myristate 13-acetate pretreatment, also suppressed the cytolytic effector function of AK-T lymphocytes. Lack of tumoricidal activity was not due to reduced AK-T lymphocyte binding to tumour target cells but was associated with the abrogation of granule exocytosis, indicating that PTK and PKC are involved in the postbinding process which results in delivery of the 'lethal hit' by AK-T lymphocytes.

Original languageEnglish
Pages (from-to)333-342
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1356
Issue number3
DOIs
Publication statusPublished - May 27 1997

Bibliographical note

Funding Information:
This work was supported by a grant to D.W.H. from the Natural Sciences and Engineering Research Council of Canada. B.H.S. is the recipient of a Medical Research Council of Canada/UpJohn Company of Canada Studentship.

ASJC Scopus Subject Areas

  • Molecular Biology
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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