3akl
Crystal structure of A Helicobacter pylori proinflammatory kinase CtkA
Structural highlights
FunctionCTKA_HELPJ Virulence factor acting as a pro-inflammatory protein that induces the secretion of the pro-inflammatory cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-8 (interleukin-8) from human macrophages, as well as enhanced translocation of the transcription factor NF-kappa-B complex in macrophages. Is a kinase capable of autophosphorylating itself at a threonine residue near the N-terminus. Also leads to enhanced phosphorylation of the NF-kappa-B p65 subunit (RELA) at 'Ser-276' in human epithelial cancer cells; its kinase activity is required for this enhanced phosphorylation that up-regulates NF-kappa-B activity, but it does not directly phosphorylate this protein. Thus, the kinase activity of CtkA may play an important role in the induction of host inflammatory responses during H.pylori infection.[1] [2] Publication Abstract from PubMedThere has been considerable interest in virulence genes in the plasticity region of Helicobacter pylori, but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of H. pylori strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-kappaB in cultured macrophages. Here we have characterized the structure and function of JHP940 to provide the framework for better understanding its role in inflammation by H. pylori. Our work demonstrates that JHP940 is the first example of a eukaryotic-type Ser/Thr kinase from H. pylori. We show that JHP940 is catalytically active as a protein kinase and translocates into cultured human cells. Furthermore, the kinase activity is indispensable for indirectly up-regulating phosphorylation of NF-kappaB p65 at Ser276. Our results, taken together, contribute significantly to understanding the molecular basis of the role of JHP940 in inflammation and subsequent pathogenesis caused by H. pylori. We propose to rename the jhp940 gene as ctkA (cell translocating kinase A). Helicobacter pylori proinflammatory protein up-regulates NF-kappaB as a cell-translocating Ser/Thr kinase.,Kim do J, Park KS, Kim JH, Yang SH, Yoon JY, Han BG, Kim HS, Lee SJ, Jang JY, Kim KH, Kim MJ, Song JS, Kim HJ, Park CM, Lee SK, Lee BI, Suh SW Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21418-23. Epub 2010 Nov 22. PMID:21098302[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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