Ultraviolet radiation rapidly induces tyrosine phosphorylation and calcium signaling in lymphocytes.
UV radiation is known to induce lymphocyte nonresponsiveness both in vitro and in vivo. We have found that UV radiation rapidly induced tyrosine phosphorylation and calcium signaling in normal human peripheral blood lymphocytes. In the leukemic T cell line Jurkat and the Burkitt's lymphoma cell line Ramos, UV rapidly induced tyrosine phosphorylation in a wavelength-dependent manner, giving strong signals after UVB and UVC, but not UVA, irradiation. Similarly, in Jurkat cells UV-induced calcium signals were dependent on the dose of UVB or UVC irradiation over a range of 150-1200 J/m2, but only a small signal was observed for UVA at a dose of 1200 J/m2. The UV-induced calcium signals were blocked by the tyrosine kinase inhibitor herbimycin A, indicating that they were dependent on tyrosine phosphorylation. Phospholipase C (PLC) gamma 1 was tyrosine phosphorylated in response to UV irradiation but to a lesser extent than observed after CD3 cross-linking. However, PLC gamma 1-associated proteins demonstrated to bind to the PLC gamma 1 SH2 domain were tyrosine phosphorylated strongly after UV irradiation. A similar dose response was observed for the inhibition by herbimycin A of UV-induced calcium signals and UV-induced tyrosine phosphorylation of PLC gamma 1 and associated proteins. We propose that in contrast to CD3/Ti stimulation, UV aberrantly triggers lymphocyte signal transduction pathways by a mechanism that bypasses normal receptor control.
Schieven
G L
GL
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Kirihara
J M
JM
Gilliland
L K
LK
Uckun
F M
FM
Ledbetter
J A
JA
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D047029:Lactams, Macrocyclic; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014466:Ultraviolet Rays
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D010738:Type C Phospholipases; D002118:Calcium