Structural highlights
Function
RIPK2_HUMAN Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.[1] [2] [3] [4]
References
- ↑ Ruefli-Brasse AA, Lee WP, Hurst S, Dixit VM. Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation. J Biol Chem. 2004 Jan 9;279(2):1570-4. Epub 2003 Nov 24. PMID:14638696 doi:http://dx.doi.org/10.1074/jbc.C300460200
- ↑ Manon F, Favier A, Nunez G, Simorre JP, Cusack S. Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK. J Mol Biol. 2007 Jan 5;365(1):160-74. Epub 2006 Sep 29. PMID:17054981 doi:10.1016/j.jmb.2006.09.067
- ↑ Hasegawa M, Fujimoto Y, Lucas PC, Nakano H, Fukase K, Nunez G, Inohara N. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J. 2008 Jan 23;27(2):373-83. Epub 2007 Dec 13. PMID:18079694 doi:http://dx.doi.org/10.1038/sj.emboj.7601962
- ↑ Tigno-Aranjuez JT, Asara JM, Abbott DW. Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 2010 Dec 1;24(23):2666-77. doi: 10.1101/gad.1964410. PMID:21123652 doi:http://dx.doi.org/10.1101/gad.1964410
