Kinome

In molecular biology, the kinome of an organism is the set of protein kinases in its genome. Kinases are 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 Manning, G, Whyte, DB, Martinez, R, Hunter, T, Sudarsanam, S (2002). The Protein Kinase Complement of the Human Genome. "Science" 298:1912-34 PMID 12471243] and the evolution of protein kinases throughout eukaryotes Manning, G, Plowman, GD, Hunter, T, Sudarsanam, S (2002). Evolution of Protein Kinase Signaling from Yeast to Man. "TiBS" 27:514-20 PMID 12368087] . Other kinomes have been determined for rice Dardick C, Chen J, Richter T, Ouyang S, Ronald P. (2006). The Rice Kinase Database. A Phylogenomic Database for the Rice Kinome. "Plant Physiol" Epub. PMID 17172291] , several fungi, nematodes, and insects, sea urchinsBradham CA, Foltz KR, Beane WS, Arnone MI, Rizzo F, Coffman JA, Mushegian A, Goel M, Morales J, Geneviere AM, Lapraz F, Robertson AJ, Kelkar H, Loza-Coll M, Townley IK, Raisch M, Roux MM, Lepage T, Gache C, McClay DR, Manning G. (2006). The sea urchin kinome: A first look. "Dev Biol" 300(1):180-93. PMID 17027740 ] and DictyosteliumGoldberg JM, Manning G, Liu A, Fey P, Pilcher KE, Xu Y, Smith JL. (2006). The dictyostelium kinome--analysis of the protein kinases from a simple model organism. "PLoS Genet" 2(3):e38. PMID 16596165 ] .

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 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. PMID 16869789 ] .

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. It was long believed that serine/threonine kinases played different metabolic roles than tyrosine kinases, the former being used mainly for inducing conformational changes versus the latter being used to create structural "handles" on proteins that to enable binding by an SH2 domain. However, recent research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and FHA domains.

References

External links

* [http://kinase.com/ Kinome site]
* [http://kinase.com/kinbase/index.html KinBase]
* [http://www.cellsignal.com/reference/kinase/kinome.html The Human Kinome diagram]
* [http://rkd.ucdavis.edu/ Rice Kinome Database]