Differential requirement of protein tyrosine kinase and protein kinase C in the generation of IL-2-induced LAK cell and alpha CD3-induced CD3-AK cell responses

Cell Immunol. 1995 Feb;160(2):286-96. doi: 10.1016/0008-8749(95)80040-p.

Abstract

This study examined the role of protein tyrosine kinase (PTK) and protein kinase C (PKC) in the signal transduction pathways for lymphocyte activation through IL-2R to generate LAK cells and through TCR-CD3 to generate CD3-AK cells. Two PTK inhibitors [herbimycin A and genistein (PTK-I)] and two PKC inhibitors [calphositin C and staurosporine (PKC-I)] were used in the experiments. It was found that the primary activation pathway through IL-2R was PTK-dependent; that is, generation of both the IL-2-induced proliferative and the cytotoxic responses was completely abrogated by PTK-I and not by PKC-I. Quite different results were obtained with the alpha CD3-induced CD3-AK cell response. First, the alpha CD3-induced proliferation was only partially inhibited by PTK-I or PKC-I alone. Second, generation of CD3-AK cytotoxic response was primarily PKC-dependent; that is, only PKC-I induced significant inhibition. Genistein was found to reduce protein tyrosine phosphorylation in both LAK cells and CD3-AK cells, indicating that CD3-AK cells were also susceptible to PTK-I treatment. Further studies showed that PTK-I and not PKC-I suppressed perforin mRNA expression and N-2-benzyoxycarbonyl-L-lysine thiobeneylester esterase production in LAK cells, and the opposite was true for CD3-AK cells. These results indicate that different pathways were employed in lymphocyte activation through IL-2R and TCR-CD3. The former pathway is primarily PTK-dependent. Activation through TCR-CD3 is a more complex event.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Benzoquinones
  • Female
  • Genistein
  • Interleukin-2 / pharmacology*
  • Isoflavones / pharmacology
  • Killer Cells, Lymphokine-Activated / drug effects
  • Killer Cells, Lymphokine-Activated / enzymology*
  • Lactams, Macrocyclic
  • Lymphocyte Activation / drug effects*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Naphthalenes*
  • Perforin
  • Polycyclic Compounds / pharmacology
  • Pore Forming Cytotoxic Proteins
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / physiology*
  • Quinones / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor-CD3 Complex, Antigen, T-Cell / physiology*
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / physiology
  • Recombinant Proteins / pharmacology
  • Rifabutin / analogs & derivatives
  • Signal Transduction*
  • Staurosporine

Substances

  • Alkaloids
  • Benzoquinones
  • Interleukin-2
  • Isoflavones
  • Lactams, Macrocyclic
  • Membrane Glycoproteins
  • Naphthalenes
  • Polycyclic Compounds
  • Pore Forming Cytotoxic Proteins
  • Quinones
  • RNA, Messenger
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Perforin
  • Rifabutin
  • herbimycin
  • Genistein
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Staurosporine
  • calphostin C