Histidine protein kinases: key signal transducers outside the animal kingdom
Genome Biology
1465-6906
Protein family review Histidine protein kinases: key signal transducers outside the animal kingdom
Histidine protein kinases (HPKs) are a large family of signal-transduction enzymes that autophosphorylate on a conserved histidine residue. HPKs form two-component signaling systems together with their downstream target proteins, the response regulators, which have a conserved aspartate in a so-called 'receiver domain' that is phosphorylated by the HPK. Twocomponent signal transduction is prevalent in bacteria and is also widely used by eukaryotes outside the animal kingdom. The typical HPK is a transmembrane receptor with an aminoterminal extracellular sensing domain and a carboxy-terminal cytosolic signaling domain; most, if not all, HPKs function as dimers. They show little similarity to protein kinases that phosphorylate serine, threonine or tyrosine residues, but may share a distant evolutionary relationship with these enzymes. In excess of a thousand known genes encode HPKs, which are important for multiple functions in bacteria, including chemotaxis and quorum sensing, and in eukaryotes, including hormone-dependent developmental processes. The proteins divide into at least 11 subfamilies, only one of which is present in eukaryotes, suggesting that lateral gene transfer gave rise to two-component signaling in these organisms.
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Summary
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The core domains
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HPK1 homology box motifs:
H box: Fhxxh(S/T/A)H(D/E)h(R/K)TPLxxh
D box: F-box: hxhxhxDxGxGhxxxxxxxhFxxF
H box
(376-394) HPK1A
(444-462) HPK1B
(234-252) HPK2
(268-286) HPK3
(130-148) HPK4
(340-358) HPK5
(408-426) HPK6
(361-379) HPK7
(373-391) HPK8
(239-257) HPK10
(367-385) HPK11
(526-551) HPK1A
(593-618) HPK1B
(367-392) HPK2
(409-434) HPK3
(281-306) HPK4
(469-494) HPK5
(535-560) HPK6
(502-520) HPK7
(500-513) HPK8
(414-460) HPK9
(390-396) HPK10
(504-517) HPK11
The sensing and linker domains
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Sensing domain
Dimerization domain Catalytic domain
TM2 HAMP
N box
D box
F box
G box
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25 amino acids
N TM1
(490-509) HPK1A
(558-577) HPK1B
(333-352) HPK2
(375-394) HPK3
(234-253) HPK4
(431-450) HPK5
(498-517) HPK6
(466-485) HPK7
(460-479) HPK8
(366-385) HPK9
(334-353) HPK10
(466-485) HPK11
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Localization and function
Transmembrane receptor HPKs
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Soluble HPKs
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3. Hoch JA , Silhavy TJ : Two-component signal transduction . Washington, D.C.: ASM Press, 1995 . A collection of reviews by experts in two-component signal transduction that is considered the starting point for most literature searches . This is still the best source of reviews for some areas, though others have become dated .
4. Fuqua C , Parsek MR , Greenberg EP : Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing . Annu Rev Genet 2001 , 35 : 439 - 468 . A review of work on quorum sensing via acylated homoserine lactones, including their production and their detection by receptor HPKs .
5. Thomason P , Kay R : Eukaryotic signal transduction via histidine-aspartate phosphorelay . J Cell Sci 2000 , 113 : 3141 - 3150 . A review of HPK systems in eukaryotes and their interaction with downstream pathways such as MAP kinase cascades and the cAMP /PKA pathway.
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7. The C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology . Science 1998 , 282 : 2012 - 2018 . Sequencing of the 97-megabase C. elegans genome was completed in 1998 and was the first genome of a multicellular organism to be fully sequenced .
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9. International Human Genome Sequencing Consortium: Initial sequencing and analysis of the human genome . Nature 2001 , 409 : 860 - 921 . A draft sequence of the human genome and intial analysis of the data .
10. Matsubara M , Kitaoka SI , Takeda SI , Mizuno T : Tuning of the porin expression under anaerobic growth conditions by His-toAsp cross-phosphorelay through both the EnvZ-osmosensor and ArcB-anaerosensor in Escherichia coli . Genes Cells 2000 , 5 : 555 - 569 . An excellent example of networking between two-component signal transduction systems .
11. Stock JB , Surette M : Chemotaxis. In Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology . Edited by Neidhardt FC. Washington, DC: ASM; 1996 : 1103 - 1129 . A detailed and thorough review of the chemotaxis system in E. coli and Salmonella, though some sections have been superseded by more recent research .
12. Dutta R , Qin L , Inouye M : Histidine kinases: diversity of domain organization . Mol Microbiol 1999 , 34 : 633 - 640 . A review and hypothesis paper that includes some speculations about HPK architecture and the interrelation between the different HPK domains .
13. Perego M , Hoch JA : Protein aspartate phosphatases control the output of two-component signal transduction systems . Trends Genet 1996 , 12 : 97 - 101 . A review of the role of HPK phosphatase activity and HPK-independent phosphatases in controlling the output of two-component systems .
14. Tanaka T , Saha SK , Tomomori C , Ishima R , Liu D , Tong KI , Park H , Dutta R , Qin L , Swindells MB , et al.: NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ . Nature 1998 , 396 : 88 - 92 . The first structural analysis of an HPK catalytic domain and demonstration of the HPK structural homology to Hsp90 and DNA gyrase B.
15. Bilwes AM , Alex LA , Crane BR , Simon MI : Structure of CheA, a signal-transducing histidine kinase . Cell 1999 , 96 : 131 - 141 . The first X-ray crystal structure of an HPK, and the only one that includes both the dimerization and catalytic domains .
16. Bilwes AM , Quezada CM , Croal LR , Crane BR , Simon MI : Nucleotide binding by the histidine kinase CheA . Nat Struct Biol 2001 , 8 : 353 - 360 . An important paper that shows the str (...truncated)
