Interleukin-7 induces T cell proliferation in the absence of Erk/MAP kinase activity

Eur J Immunol. 1996 Nov;26(11):2717-23. doi: 10.1002/eji.1830261125.

Abstract

Interleukin (IL)-7 and IL-2 are important lymphoproliferative cytokines which both use the gamma c chain as part of their respective receptors. To learn more of their signaling mechanisms a comparison was made of the patterns of intracellular tyrosine phosphorylated proteins induced by these cytokines in the murine T cell line, CT6. Several similarities were revealed in the tyrosine phosphorylated proteins induced. However, a notable subset of proteins of mainly < 60 kDa were only phosphorylated by IL-2. Characterization of the two most prominent bands of this subset, pp54 and pp42, revealed these to contain Shc and p42MAP/Erk kinase, respectively. Further studies confirmed that IL-7 was unable to induce the phosphorylation of either the p44MAP/Erk or p42MAP/Erk or activation of the kinases. Shc is involved in activation of p21ras, a key event in the signaling cascade, via p72raf and MEK, leading to MAP/Erk kinase (MAPK) activation. These data indicate that this pathway is not utilized by IL-7 and may not, therefore, be essential for cytokine-driven T cell proliferation. This possibility was supported by studies with the MEK inhibitor PD098059, which had no selective effect on CT6 proliferation induced by IL-2 as compared with IL-7, although the drug completely inhibited MAP/Erk phosphorylation induced by IL-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Enzyme Activation / immunology
  • Insulin Receptor Substrate Proteins
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology*
  • Lymphocyte Activation / drug effects*
  • MAP Kinase Kinase 1
  • Mice
  • Mitogen-Activated Protein Kinase Kinases*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / analysis
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / metabolism*
  • Protein-Tyrosine Kinases / physiology
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Insulin Receptor Substrate Proteins
  • Interleukin-2
  • Interleukin-7
  • Irs1 protein, mouse
  • Phosphoproteins
  • Proto-Oncogene Proteins c-myc
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases