Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis.
Radiation-induced biochemical events that mediate the intracellular signal transduction leading to cell apoptosis are largely unknown. Limited evidence suggests the possible involvement of one or more protein-tyrosine kinases (PTKs) in radiation-induced cellular responses, including apoptosis. However, so far, a PTK(s) responsible for the radiation-induced tyrosine phosphorylation of cellular substrates has not been identified and the role of the PTK(s) in the radiation-induced apoptosis remains unclear. To examine the roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we analyzed Syk-deficient or Lyn-deficient DT40 B cells along with wild-type cells following radiation. When DT40 B cells were exposed to radiation, the activity of Syk kinase dramatically increased and reached a maximum with 0.25 Grays (Gy) (15 s), and then decreased, whereas Lyn kinase activity increased and reached a maximum with a dose of 1.00 Gy (1 min). However, an apparent difference was not observed in radiation-induced apoptosis among wild-type, Syk-deficient, and Lyn-deficient DT40 B cells. These results indicate that Syk and Lyn kinases are involved in radiation-induced signal transduction, with different kinetics. In addition, our results revealed that functional inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis. Thus, it is suggested that the activation of Syk or Lyn kinase alone may be sufficient to mediate the radiation-induced apoptosis in DT40 B cells, or both kinases may not be required for this biological process.
Department of Biochemistry, Fukui Medical School.
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C
Yang
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Maruyama
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Yanagi
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Wang
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Takata
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Kurosaki
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Yamamura
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001402:B-Lymphocytes / Q000201:enzymology / Q000528:radiation effects*; D002460:Cell Line; D002645:Chickens; D004789:Enzyme Activation / Q000528:radiation effects; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000528:radiation effects*; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases