<i>Helicobacter pylori</i>
            proinflammatory protein up-regulates NF-κB as a cell-translocating Ser/Thr kinase

Kim, Dojin; Park, Kang Seo; Kim, Jung Ho; Yang, Soo Jung; Yoon, Ji Young; Han, Byeong Gu; Kim, Hyoun Sook; Lee, Sang Jae; Jang, Jun Young; Kim, Kyoung Hoon; Kim, Mi Jung; Song, Jin Su; Kim, Hie Joon; Park, Chung Mo; Lee, Sang Kyou; Lee, Byung Il; Suh, Se Won

doi:10.1073/pnas.1010153107

Cited by 51 publications

(52 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the atypical type II kinases are structurally more similar to protein Ser/Thr kinases than to other lipid kinases. Analysis by the DALI server [82] reveals that their overall structure most closely resembles the cell translocating kinase A (ctkA) from the bacterium Helicobacter pylori [83]. The structural similarity becomes more profound when the comparison is done separately for the N-and C-lobe of the kinase domain.…”

Section: Structural Biology Of Pi4ksmentioning

confidence: 99%

Phosphatidylinositol 4-kinases: Function, structure, and inhibition

Bouřa

Nencka

2015

Experimental Cell Research

130

107

View full text Add to dashboard Cite

Section: Structural Biology Of Pi4ksmentioning

confidence: 99%

Phosphatidylinositol 4-kinases: Function, structure, and inhibition

Bouřa

Nencka

2015

Experimental Cell Research

130

107

View full text Add to dashboard Cite

“…3B). This Lys is not commonly present in canonical kinases but is found in HipA and CtkA, two bacterial kinases that are remotely related to the Fam20 family (7,35,36).…”

Section: Resultsmentioning

confidence: 99%

Crystal structure of the Golgi casein kinase

Xiao

Tagliabracci

Wen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The family with sequence similarity 20 (Fam20) kinases phosphorylate extracellular substrates and play important roles in biomineralization. Fam20C is the Golgi casein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs. Mutations in Fam20C cause Raine syndrome, an osteosclerotic bone dysplasia. Here we report the crystal structure of the Fam20C ortholog from Caenorhabditis elegans. The nucleotide-free and Mn/ ADP-bound structures unveil an atypical protein kinase-like fold and highlight residues critical for activity. The position of the regulatory αC helix and the lack of an activation loop indicate an architecture primed for efficient catalysis. Furthermore, several distinct elements, including the presence of disulfide bonds, suggest that the Fam20 family diverged early in the evolution of the protein kinase superfamily. Our results reinforce the structural diversity of protein kinases and have important implications for patients with disorders of biomineralization.P rotein phosphorylation is a fundamental mechanism that regulates numerous physiological processes (1, 2). Protein kinases have evolved to function as dynamic switches relaying signals in response to various stimuli by transferring a phosphate from ATP to target proteins (3-5). Most phosphoproteins are found within the cell, residing in the nuclei and cytosol; however, secreted proteins, including casein and other members of the secretory calciumbinding phosphoprotein family, are phosphorylated as well (6). We recently identified a family of kinases that reside in the secretory pathway and function to phosphorylate extracellular substrates (7,8). One member of this family, Fam20C (family with sequence similarity 20, member C), is the physiological casein kinase that phosphorylates multiple secreted proteins within a Ser-x-Glu/pSer motif (7, 9, 10). The importance of this discovery is underscored by the fact that some 75% of the phosphoproteins identified in human serum and cerebrospinal fluid contain phosphate within this motif (11-13). Furthermore, mutations in FAM20C cause Raine syndrome, a deadly osteosclerotic bone dysplasia characterized by generalized osteosclerosis, ectopic calcifications, and characteristic facial features (14-16). Most individuals with Raine syndrome die within a few weeks after birth; however, nonlethal cases with dental abnormalities and clinical features of hypophosphatemia have been reported (17,18). Loss of Fam20C in mice also results in severe bone and tooth anomalies, as well as hypophosphatemia (19)(20)(21).Two other closely related Fam20C paralogs, Fam20A and Fam20B, are present in humans (22). Fam20B is ubiquitously expressed and phosphorylates xylose within the tetrasaccharide linkage region of proteoglycans (23). This phosphorylation event may influence glycosaminoglycan biosynthesis (24). Genetic deletion of Fam20B in mice results in embryonic lethality at E13.5, and mutations in Danio rerio result in reduced cartilage matrix production and skeletal defects (19,25). The substra...

show abstract

“…In contrast, bacterial kinases frequently modify His residues on proteins as part of a two-component system (2). Nevertheless, prokaryotic kinases, such as the bacterial persistence kinase, high-persistence factor A (HipA), and the proinflammatory kinase, cell translocating kinase A (CtkA), can modify Ser and Thr residues on proteins as well (3,4).…”

mentioning

confidence: 99%

Phosphorylation of spore coat proteins by a family of atypical protein kinases

Nguyen

Sreelatha

Durrant

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The modification of proteins by phosphorylation occurs in all life forms and is catalyzed by a large superfamily of enzymes known as protein kinases. We recently discovered a family of secretory pathway kinases that phosphorylate extracellular proteins. One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase. While examining distantly related protein sequences, we observed low levels of identity between the spore coat protein H (CotH), and the Fam20C-related secretory pathway kinases. CotH is a component of the spore in many bacterial and eukaryotic species, and is required for efficient germination of spores in Bacillus subtilis; however, the mechanism by which CotH affects germination is unclear. Here, we show that CotH is a protein kinase. The crystal structure of CotH reveals an atypical protein kinase-like fold with a unique mode of ATP binding. Examination of the genes neighboring cotH in B. subtilis led us to identify two spore coat proteins, CotB and CotG, as CotH substrates. Furthermore, we show that CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores. Collectively, our results define a family of atypical protein kinases and reveal an unexpected role for protein phosphorylation in spore biology.

show abstract

Helicobacter pylori proinflammatory protein up-regulates NF-κB as a cell-translocating Ser/Thr kinase

Cited by 51 publications

References 30 publications

Phosphatidylinositol 4-kinases: Function, structure, and inhibition

Phosphatidylinositol 4-kinases: Function, structure, and inhibition

Crystal structure of the Golgi casein kinase

Phosphorylation of spore coat proteins by a family of atypical protein kinases

Contact Info

Product

Resources

About