Signaling through ephrin-A ligand leads to activation of Src-family kinases, Akt phosphorylation, and inhibition of antigen receptor-induced apoptosis.
Eph receptor tyrosine kinases and ephrins play important roles in diverse biological processes such as migration, adhesion, and angiogenesis. Forward and reverse signaling has been reported in receptor- and ligand-bearing cells. The ligands can be divided into the transmembrane ephrin-B family and the GPI-anchored ephrin-A family. Here, we show expression of ephrin-A ligands on CD4+ T cells cultured in medium with human serum and the T cell line Jurkat TAg and on cells isolated from patients with T cell lymphomas and T cell leukemias. Functional role and identification of proteins involved in ephrin-A signaling were investigated here in the T cell line Jurkat TAg. Signaling through ephrin-A induces phosphorylation of several proteins, including the Src kinases Lck and Fyn. In addition, PI-3K is activated, shown by induced phosphorylation of the Akt kinase. An ephrin-A signaling complex could be isolated, containing several phosphorylated proteins including Lck and Fyn. Interestingly, we show that signaling through ephrin-A in Jurkat TAg cells, initiated by interaction with the EphA2 receptor, leads to inhibition of activation-induced cell death. To conclude, ephrin-A signaling in Jurkat TAg cells leads to induced phosphorylation of several proteins including Lck, Fyn, and Akt. A consequence of ephrin-A signaling is inhibition of antigen receptor-induced apoptosis.
Holen
Halvor L
HL
Ullevaal University Hospital, 0407 Oslo, Norway.
Shadidi
Mohsen
M
Narvhus
Kristina
K
Kjøsnes
Oddveig
O
Tierens
Anne
A
Aasheim
Hans-Christian
HC
D017209:Apoptosis / Q000502:physiology*; D004261:DNA Replication; D004789:Enzyme Activation; D036342:Ephrins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011946:Receptors, Antigen / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D036342:Ephrins; D008024:Ligands; D034741:RNA, Small Interfering; D011946:Receptors, Antigen; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt