EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion

Exp Cell Res. 2004 Jan 15;292(2):295-303. doi: 10.1016/j.yexcr.2003.08.021.

Abstract

Stimulation of CD28 alone has been shown to regulate cytokine gene transcription and expression of the type 1 insulin-like growth factor receptor (IGF-1R) in lymphocytes. In this study, the ephrin receptor tyrosine kinase ephA3, was identified as a new CD28-responsive gene in Jurkat cells by using a human cytokine/receptor array. EphA3 was not detected in normal peripheral T cells, in any subset of thymus-derived developing T cells, or in Hodgkin's lymphoma. However, contrary to previous findings, EphA3 was detected in a panel of T-cell lymphomas. Stimulation of Jurkat cells with ephrin-A5 resulted in loss of cell adhesion to fibronectin and recruitment of the adapter protein CrkII to EphA3. Interestingly, EphA3 expression in CD28-stimulated Jurkat cells was enhanced by IGF-1 or by overexpression of the IGF-1R, and was suppressed by anti-IGF-1R blocking antibodies. The data suggest that CD28- and IGF-1-regulated expression of EphA3 is associated with adherence and that it may be involved in the motility of malignant T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • CD28 Antigens / metabolism*
  • CD28 Antigens / pharmacology
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Ephrin-A5 / metabolism
  • Ephrin-A5 / pharmacology
  • Fibronectins / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / pharmacology
  • Jurkat Cells
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / metabolism*
  • Neoplasm Metastasis / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-crk
  • Reaction Time / drug effects
  • Reaction Time / genetics
  • Receptor, EphA3 / metabolism*
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Antibodies
  • CD28 Antigens
  • Ephrin-A5
  • Fibronectins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Insulin-Like Growth Factor I
  • Receptor, EphA3
  • Receptor, IGF Type 1