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

Autor: David W. Hoskin, B H Stewart
Rok vydání: 1997
Předmět:
Lactams
Macrocyclic
Lymphocyte
Anti-CD3 antibody
Biology
Granzymes
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Protein kinase C
Neoplasms
Benzoquinones
medicine
Animals
Cytotoxic T cell
Staurosporine
Calphostin
Protein tyrosine kinase
Molecular Biology
030304 developmental biology
0303 health sciences
Cytotoxic T lymphocyte
Serine Endopeptidases
Antibody-Dependent Cell Cytotoxicity
Quinones
Cell Biology
Protein-Tyrosine Kinases
MHC-unrestricted cytotoxicity
Genistein
Isoflavones
Molecular biology
Cell biology
Killer Cells
Natural
Mice
Inbred C57BL
medicine.anatomical_structure
Rifabutin
chemistry
Granzyme
Cinnamates
030220 oncology & carcinogenesis
Phorbol
biology.protein
Female
Signal transduction
Immunosuppressive Agents
Muromonab-CD3
Signal Transduction
medicine.drug
Zdroj: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1356(3):333-342
ISSN: 0167-4889
DOI: 10.1016/s0167-4889(97)00003-7
Popis: 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. © 1997 Elsevier Science B.V. All rights reserved.
Databáze: OpenAIRE
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