EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion.
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.
Smith
Loraine M
LM
Department of Biochemistry, Biosciences Institute, National University of Ireland, Cork, Ireland.
Walsh
Patrick T
PT
Rüdiger
Thomas
T
Cotter
Thomas G
TG
Mc Carthy
Tommie V
TV
Marx
Alexander
A
O'Connor
Rosemary
R
D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D036386:Ephrin-A5 / Q000378:metabolism / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050737:Proto-Oncogene Proteins c-crk; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D036121:Receptor, EphA3 / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000906:Antibodies; D018106:CD28 Antigens; D036386:Ephrin-A5; D005353:Fibronectins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D007334:Insulin-Like Growth Factor I; D036121:Receptor, EphA3; D017526:Receptor, IGF Type 1