Tyrosine kinase(s) regulate apoptosis and bcl-2 expression in a growth factor-dependent cell line

J Biol Chem. 1993 Oct 25;268(30):22733-6.

Abstract

Apoptosis (programmed cell death) plays a critical role in many physiological processes, but the mechanism(s) which regulate apoptosis are poorly understood. We demonstrate that in a hematopoietic cell line, which can grow in either interleukin (IL)-2 or IL-3, both of these growth factors can increase bcl-2 mRNA levels and prevent apoptosis normally seen following growth factor withdrawal. Herbimycin A, a protein tyrosine kinase inhibitor, blocks the ability of IL-2 and IL-3 to up-regulate bcl-2 mRNA levels and induces apoptosis. Transfection of a bcl-2 expression vector not only prolongs survival following growth factor withdrawal but also confers resistance to the effect of herbimycin A. We conclude that herbimycin A-sensitive protein tyrosine kinases are involved in the regulation of apoptosis and bcl-2 expression, but these protein tyrosine kinases appear not to be required for the action of Bcl-2 since Bcl-2 can exert its growth survival effect even in the presence of herbimycin A.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Benzoquinones
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Culture Media, Conditioned
  • Electroporation
  • Gene Expression Regulation, Enzymologic*
  • Growth Substances / pharmacology*
  • Humans
  • Interleukin-2 / pharmacology
  • Interleukin-3 / pharmacology
  • Kinetics
  • Lactams, Macrocyclic
  • Mice
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • Quinones / toxicity
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Rifabutin / analogs & derivatives

Substances

  • Benzoquinones
  • Culture Media, Conditioned
  • Growth Substances
  • Interleukin-2
  • Interleukin-3
  • Lactams, Macrocyclic
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Quinones
  • RNA, Messenger
  • Recombinant Proteins
  • Rifabutin
  • herbimycin
  • Protein-Tyrosine Kinases