Syk is required for the activation of Akt survival pathway in B cells exposed to oxidative stress.
Syk has been demonstrated to play a crucial role in oxidative stress signaling in B cells. Here we report that Syk is required for the activation of the phosphatidylinositol (PI) 3-kinase-Akt survival pathway in B cells exposed to oxidative stress. Phosphorylation and activation of the serine-threonine kinase Akt were markedly increased in B cells treated with H(2)O(2). In Syk-deficient DT40 cells treated with low doses of H(2)O(2) (10-100 microm), Akt activation was considerably reduced. Pretreatment with wortmannin, a PI 3-kinase-specific inhibitor, completely blocked the Syk-dependent Akt activation. Following stimulation by low doses of H(2)O(2), a significant increase in PI 3-kinase activity was found in wild-type but not in Syk-deficient cells. These findings suggest that PI 3-kinase mediates Syk-dependent Akt activation pathway. Furthermore, viability of Syk-deficient cells, after exposure to H(2)O(2), was dramatically decreased and caspase-9 activity was greatly increased compared with that of the wild-type cells. These results suggest that Syk is essential for the Akt survival pathway in B cells and enhances cellular resistance to oxidative stress-induced apoptosis.
Ding
J
J
Department of Biochemistry, Kobe University School of Medicine, Kobe 650-0017, Japan and Hyogo College, Kakogawa, 675-0101, Japan.
Takano
T
T
Gao
S
S
Han
W
W
Noda
C
C
Yanagi
S
S
Yamamura
H
H
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism* / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013552:Swine; D000072377:Syk Kinase; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D053453:Caspase 9; D020169:Caspases; D004792:Enzyme Precursors; D006861:Hydrogen Peroxide; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000072377:Syk Kinase; D000077191:Wortmannin