TNF-stimulated MAP Kinase Activation Mediated by a Rho Family GTPase Signaling Pathway

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2011 Oct 8

PMID 21979919

Citations 64

Authors

Shashi Kant

Wojciech Swat

Sheng Zhang

Zhong-Yin Zhang

Benjamin G Neel

Richard A Flavell

Roger J Davis

Affiliations

Soon will be listed here.

Abstract

The biological response to tumor necrosis factor (TNF) involves activation of MAP kinases. Here we report a mechanism of MAP kinase activation by TNF that is mediated by the Rho GTPase family members Rac/Cdc42. This signaling pathway requires Src-dependent activation of the guanosine nucleotide exchange factor Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site (CRIB motif) on mixed-lineage protein kinases (MLKs). We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo.

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References

Coso O, Chiariello M, Yu J, Teramoto H, Crespo P, Xu N . The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995; 81(7):1137-46. DOI: 10.1016/s0092-8674(05)80018-2. View

Kim B, Lee M, Kim J, Lee S, Chang J, Kim S . Roles of phosphatidylinositol 3-kinase and Rac in the nuclear signaling by tumor necrosis factor-alpha in rat-2 fibroblasts. J Biol Chem. 1999; 274(34):24372-7. DOI: 10.1074/jbc.274.34.24372. View

Tournier C, Hess P, Yang D, Xu J, Turner T, Nimnual A . Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science. 2000; 288(5467):870-4. DOI: 10.1126/science.288.5467.870. View

Song J, Arudchandran R, Gomez J, Scott P, Mill J, Tan T . Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway. J Immunol. 1999; 163(2):802-10. View

Garcia-Mata R, Wennerberg K, Arthur W, Noren N, Ellerbroek S, Burridge K . Analysis of activated GAPs and GEFs in cell lysates. Methods Enzymol. 2006; 406:425-37. DOI: 10.1016/S0076-6879(06)06031-9. View

Ramakrishnan P, Baltimore D . Sam68 is required for both NF-κB activation and apoptosis signaling by the TNF receptor. Mol Cell. 2011; 43(2):167-79. PMC: 3142289. DOI: 10.1016/j.molcel.2011.05.007. View

Micheau O, Tschopp J . Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003; 114(2):181-90. DOI: 10.1016/s0092-8674(03)00521-x. View

Tuyt L, Dokter W, Birkenkamp K, Koopmans S, Lummen C, Kruijer W . Extracellular-regulated kinase 1/2, Jun N-terminal kinase, and c-Jun are involved in NF-kappa B-dependent IL-6 expression in human monocytes. J Immunol. 1999; 162(8):4893-902. View

Teramoto H, Coso O, Miyata H, Igishi T, Miki T, Gutkind J . Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. A role for mixed lineage kinase 3/protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family. J Biol Chem. 1996; 271(44):27225-8. DOI: 10.1074/jbc.271.44.27225. View

10.

Minden A, Lin A, Claret F, Abo A, Karin M . Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell. 1995; 81(7):1147-57. DOI: 10.1016/s0092-8674(05)80019-4. View

11.

Zhang S, Chen L, Luo Y, Gunawan A, Lawrence D, Zhang Z . Acquisition of a potent and selective TC-PTP inhibitor via a stepwise fluorophore-tagged combinatorial synthesis and screening strategy. J Am Chem Soc. 2009; 131(36):13072-9. PMC: 2741613. DOI: 10.1021/ja903733z. View

12.

Kim Y, Morgan M, Choksi S, Liu Z . TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell. 2007; 26(5):675-87. DOI: 10.1016/j.molcel.2007.04.021. View

13.

Ichijo H, Nishida E, Irie K, Ten Dijke P, Saitoh M, Moriguchi T . Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997; 275(5296):90-4. DOI: 10.1126/science.275.5296.90. View

14.

Skaug B, Jiang X, Chen Z . The role of ubiquitin in NF-kappaB regulatory pathways. Annu Rev Biochem. 2009; 78:769-96. DOI: 10.1146/annurev.biochem.78.070907.102750. View

15.

Shim J, Xiao C, Paschal A, Bailey S, Rao P, Hayden M . TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 2005; 19(22):2668-81. PMC: 1283960. DOI: 10.1101/gad.1360605. View

16.

Han J, Das B, Wei W, Van Aelst L, Mosteller R, Khosravi-Far R . Lck regulates Vav activation of members of the Rho family of GTPases. Mol Cell Biol. 1997; 17(3):1346-53. PMC: 231859. DOI: 10.1128/MCB.17.3.1346. View

17.

Liu B, Burridge K . Vav2 activates Rac1, Cdc42, and RhoA downstream from growth factor receptors but not beta1 integrins. Mol Cell Biol. 2000; 20(19):7160-9. PMC: 86269. DOI: 10.1128/MCB.20.19.7160-7169.2000. View

18.

Lamb J, Ventura J, Hess P, Flavell R, Davis R . JunD mediates survival signaling by the JNK signal transduction pathway. Mol Cell. 2003; 11(6):1479-89. DOI: 10.1016/s1097-2765(03)00203-x. View

19.

Das M, Sabio G, Jiang F, Rincon M, Flavell R, Davis R . Induction of hepatitis by JNK-mediated expression of TNF-alpha. Cell. 2009; 136(2):249-60. PMC: 2794880. DOI: 10.1016/j.cell.2008.11.017. View

20.

Abe K, Rossman K, Liu B, Ritola K, Chiang D, Campbell S . Vav2 is an activator of Cdc42, Rac1, and RhoA. J Biol Chem. 2000; 275(14):10141-9. DOI: 10.1074/jbc.275.14.10141. View