Kinome

In molecular biology, biochemistry and cell signaling the kinome of an organism is the complete set of protein kinases encoded in its genome. Kinases are usually enzymes that catalyze phosphorylation reactions (of amino acids) and fall into several groups and families, e.g., those that phosphorylate the amino acids serine and threonine, those that phosphorylate tyrosine and some that can phosphorylate both, such as the MAP2K and GSK families. The term was first used in 2002 by Gerard Manning and colleagues in twin papers analyzing the 518 human protein kinases, and refers to both protein kinases and protein pseudokinases [1] and their evolution of protein kinases throughout the eukaryotes.[2] Other kinomes have been determined for rice,[3] several fungi, nematodes, and insects, sea urchins,[4] Dictyostelium discoideum,[5] and the process of infection by Mycobacterium tuberculosis.[6] Although the primary sequence of protein kinases shows substantial divergence between unrelated eukaryotes, and amino acid differences in catalytic motifs have permitted their separation of kinomes into canonical and pseudokinase subtypes,[7] the variation found in the amino acid motifs adjacent to the site of actual phosphorylation of substrates by eukaryotic kinases is much smaller.[8]

This article is about the term in molecular biology. For the plant and food, see Zanthoxylum piperitum.

As kinases are a major drug target and a major control point in cell behavior, the kinome has also been the target of large scale functional genomics with RNAi screens and of drug discovery efforts, especially in cancer therapeutics.[9]

In animals, the kinome includes kinases that phosphorylate only tyrosine (tyrosine kinases), those that act on serine or threonine, and a few classes, such as GSK3 and MAP2K that can act on both. Research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and FHA domains.

See also

References
  1. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome". Science. 298 (5600): 1912–34. doi:10.1126/science.1075762. PMID 12471243.
  2. Manning G, Plowman GD, Hunter T, Sudarsanam S (October 2002). "Evolution of protein kinase signaling from yeast to man". Trends Biochem. Sci. 27 (10): 514–20. doi:10.1016/S0968-0004(02)02179-5. PMID 12368087.
  3. Dardick C, Chen J, Richter T, Ouyang S, Ronald P (February 2007). "The Rice Kinase Database. A Phylogenomic Database for the Rice Kinome". Plant Physiol. 143 (2): 579–86. doi:10.1104/pp.106.087270. PMC 1803753. PMID 17172291.
  4. Bradham CA, Foltz KR, Beane WS, et al. (December 2006). "The sea urchin kinome: a first look". Dev. Biol. 300 (1): 180–93. doi:10.1016/j.ydbio.2006.08.074. PMID 17027740.
  5. Goldberg JM, Manning G, Liu A, et al. (March 2006). "The Dictyostelium Kinome—Analysis of the Protein Kinases from a Simple Model Organism". PLoS Genet. 2 (3): e38. doi:10.1371/journal.pgen.0020038. PMC 1420674. PMID 16596165.
  6. Hestvik AL, Hmama Z, Av-Gay Y (October 2003). "Kinome Analysis of Host Response to Mycobacterial Infection: a Novel Technique in Proteomics". Infect. Immun. 71 (10): 5514–22. doi:10.1128/IAI.71.10.5514-5522.2003. PMC 201077. PMID 14500469.
  7. Reiterer V, Eyers PA, Farhan H (2014). "Day of the dead: pseudokinases and pseudophosphatases in physiology and disease". Trends in Cell Biology. 24 (9): 489–505. doi:10.1016/j.tcb.2014.03.008. PMID 24818526.
  8. Diks SH, Parikh K, van der Sijde M, Joore J, Ritsema T, Peppelenbosch MP (2007). Insall R (ed.). "Evidence for a Minimal Eukaryotic Phosphoproteome?". PLoS ONE. 2 (1): 777. doi:10.1371/journal.pone.0000777. PMC 1945084. PMID 17712425.
  9. Workman P (2005). "Drugging the cancer kinome: progress and challenges in developing personalized molecular cancer therapeutics". Cold Spring Harb. Symp. Quant. Biol. 70: 499–515. doi:10.1101/sqb.2005.70.020. PMID 16869789.
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