Editors' ChoiceCell Biology

Sensing H2O2 with Syk and Lyn

Sci. Signal.  27 Oct 2015:
Vol. 8, Issue 400, pp. ec308
DOI: 10.1126/scisignal.aad7102

At low amounts, reactive oxygen species (ROS), for example hydrogen peroxide (H2O2), can stimulate signaling, such as through activation of the nonreceptor tyrosine kinase Lyn. Although activation of the nonreceptor tyrosine kinase Syk by Lyn is best characterized as a response to B cell receptor activation, Patterson et al. linked Syk and Lyn to responses to H2O2 in cells of both hematopoietic and nonhematopoietic origin. Pharmacological inhibition of Syk in primary mouse splenic B cells or mouse embryonic fibroblasts (MEFs) or genetic deficiency of Syk in DT40 B cells reduced to varying degrees the phosphorylation of tyrosine, serine, or threonine residues in the kinases Btk, JNK, and Akt; phospholipase C γ2 (PLCγ2); and proteins involved in cellular processes, including transcription, translation, and metabolism. Activation of Syk by H2O2 in primary B cells and MEFs required Lyn, not protein tyrosine phosphatases, which are inactivated by ROS. Inhibition of complex I of the respiratory chain in mitochondria prevented the activation of Lyn and Syk by H2O2 in primary B cells, MEFs, or DT40 cells, but not by B cell receptor ligation in primary B cells or DT40 cells. H2O2 induced the tyrosine phosphorylation of a pool of Lyn and Syk that was located in the mitochondrial intermembrane space. Bioinformatics analysis indicated that Syk was present in many human tissues and that Syk was evolutionarily conserved in vertebrates, suggesting that this pathway could mediate cellular responses to H2O2 in many cell types and organisms.

H. C. Patterson, C. Gerbeth, P. Thiru, N. F. Vögtle, M. Knoll, A. Shahsafaei, K. E. Samocha, C. X. Huang, M. M. Harden, R. Song, C. Chen, J. Kao, J. Shi, W. Salmon, Y. D. Shaul, M. P. Stokes, J. C. Silva, G. W. Bell, D. G. MacArthur, J. Ruland, C. Meisinger, H. F. Lodish, A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling. Proc. Natl. Acad. Sci. U.S.A. 112, E5679–E5688 (2015). [PubMed]