Syk is required for p38 activation and G2/M arrest in B cells exposed to oxidative stress.
Syk has been demonstrated to play a crucial role in oxidative stress signaling in B cells. In this study, we have investigated the role of Syk in p38 activation and the regulation of cell-cycle progression upon oxidative stress. In B cells, p38 is activated by hydrogen peroxide (H(2)O(2)) stimulation. Syk is required for p38 activation following stimulation with 10-100 microM H(2)O(2), but not with 1 mM H(2)O(2). H(2)O(2)-induced p38 activation is abrogated in phospholipase C-gamma2 (PLC-gamma2)-deficient as well as Syk-deficient cells, suggesting that Syk activates p38 through PLC-gamma2 upon H(2)O(2) stimulation. Although stimulation with 20-100 microM H(2)O(2) induces cellular apoptosis in B cells, pretreatment with SB203580, a p38-specific inhibitor, has no effect on H(2)O(2)-induced apoptosis. Flow cytometric analysis reveals that B cells exposed to 10-20 microM H(2)O(2) exhibit cell-cycle profile of G2/M arrest, and pretreatment with SB203580 inhibits only a little H(2)O(2)-induced G2/M arrest. On the other hand, Syk-deficient cells show no induction of G2/M arrest following H(2)O(2) stimulation. These findings indicate that Syk plays a role in the regulation of cell-cycle progression in G2/M phase via p38-dependent and -independent pathways after oxidative stress.
He
Jinsong
J
Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Takano
Tomoko
T
Ding
Junyi
J
Gao
Sanyang
S
Noda
Chiseko
C
Sada
Kiyonao
K
Yanagi
Shigeru
S
Yamamura
Hirohei
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002470:Cell Survival; D002645:Chickens; D053938:DNA Fragmentation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D051966:Phospholipase C gamma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D000072377:Syk Kinase; D010738:Type C Phospholipases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D016877:Oxidants; D011725:Pyridines; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C093642:SB 203580