» Articles » PMID: 15456887

Germinal Center Kinase is Required for Optimal Jun N-terminal Kinase Activation by Toll-like Receptor Agonists and is Regulated by the Ubiquitin Proteasome System and Agonist-induced, TRAF6-dependent Stabilization

Overview
Journal Mol Cell Biol
Specialty Cell Biology
Date 2004 Oct 1
PMID 15456887
Citations 19
Authors
Affiliations
Soon will be listed here.
Abstract

Germinal center kinase (GCK), a member of the Ste20 family, selectively activates the Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases. Here, we show that endogenous GCK is activated by polyinosine-polycytidine [poly(IC)] and lipopolysaccharides (LPS), lipid A, interleukin-1 (IL-1), and engagement of CD40, all agonists that require TRAF6 for JNK activation. RNA interference experiments indicate that GCK is required for the maximal activation of JNK by LPS, lipid A, poly(IC), and, to a lesser extent, IL-1 and engagement of CD40. GCK is ubiquitinated in situ and stabilized by inhibitors of the proteasome, indicating that GCK is subject to proteasomal turnover. GCK is constitutively active, and the kinase activity of GCK is required for GCK ubiquitination. Agonist activation of GCK involves the TRAF6-dependent transient stabilization of the GCK polypeptide rather than an increase in intrinsic kinase activity. Our results identify a physiologic function and unexpected mode of regulation for GCK.

Citing Articles

Versatile whey acidic protein four-disulfide core domain proteins: biology and role in diseases.

Wen Y, Jiang N, Wang Z, Xiao Y Front Cell Dev Biol. 2024; 12:1459129.

PMID: 39296934 PMC: 11408880. DOI: 10.3389/fcell.2024.1459129.


Development of an optogenetics tool, Opto-RANK, for control of osteoclast differentiation using blue light.

Takada A, Asano T, Nakahama K, Ono T, Nakata T, Ishii T Sci Rep. 2024; 14(1):1749.

PMID: 38242937 PMC: 10799070. DOI: 10.1038/s41598-024-52056-w.


Hippo pathway in intestinal diseases: focusing on ferroptosis.

Deng H, Jia Q, Ming X, Sun Y, Lu Y, Liu L Front Cell Dev Biol. 2023; 11:1291686.

PMID: 38130953 PMC: 10734691. DOI: 10.3389/fcell.2023.1291686.


MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway.

Lu J, Hu Z, Deng Y, Wu Q, Wu M, Song H J Biol Chem. 2021; 296:100400.

PMID: 33571521 PMC: 7948509. DOI: 10.1016/j.jbc.2021.100400.


HOPS/Tmub1 involvement in the NF-kB-mediated inflammatory response through the modulation of TRAF6.

Bellet M, Pieroni S, Castelli M, Piobbico D, Fallarino F, Romani L Cell Death Dis. 2020; 11(10):865.

PMID: 33060567 PMC: 7567074. DOI: 10.1038/s41419-020-03086-5.


References
1.
Dumitru C, Ceci J, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin J . TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell. 2001; 103(7):1071-83. DOI: 10.1016/s0092-8674(00)00210-5. View

2.
Yeh W, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A . Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity. 1997; 7(5):715-25. DOI: 10.1016/s1074-7613(00)80391-x. View

3.
Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K . ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2001; 2(3):222-8. PMC: 1083842. DOI: 10.1093/embo-reports/kve046. View

4.
Elbashir S, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T . Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001; 411(6836):494-8. DOI: 10.1038/35078107. View

5.
Wang C, Deng L, Hong M, Akkaraju G, Inoue J, Chen Z . TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001; 412(6844):346-51. DOI: 10.1038/35085597. View