Kinase Family PVR
Kinase Classification: Group TK: Family PVR
These growth factor receptors signal during angiogenesis and other tissue growth responses.
In humans, it consists of three subfamilies:
Subfamily Kit
Contains kit, Flt3 and fms/CSF1R
Subfamily PDGFR
Contains PDGFRa and PDGFRb
Subfamily VEGFR
Contains VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4)
Evolution
PVRs are found many metazoans, including insects and vertebrates, and maybe in nematodes. Within the chordates, it appears that a tandem triplication of a single PVR gene gave rise to the founding members of the Kit, PDGFR, and VEGFR subfamilies, which then later expanded during the whole genome duplications early in vertebrate evolution [1]. The first distinctive Kit and PDGFR genes are found in hagfish [2]. The KIN16 family of C. elegans RTKs may also be members of the PVR family.
Domain Structure
PVRs are transmembrane receptors containing a signal peptide, followed by an array of immunoglobulin repeats, a transmembrane region, and a kinase domain. VEGFRs have seven Ig domains, while Kit and PDGFR subfamilies have five.
Classification History
The PDGFR and Kit subfamilies were generally classified as the PDGFR family in several major classifications [3, 4]. The newer classification which splits Kit and PDGFR as subfamilies, and adds VEGFR as another PVR subfamily was adopted by KinBase in August 2011. Pre-chordate PVR genes are similar to all three vertebrate families, and are classified as VEGFR to reflect their general conservation of 7 Ig domains in their extracellular region, whereas Kit and PDGFR have only 5.
Function
See subfamilies for functional details.
References
- Siegel N, Hoegg S, Salzburger W, Braasch I, and Meyer A. Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications. BMC Genomics. 2007 Sep 6;8:312. DOI:10.1186/1471-2164-8-312 |
- Suga H, Hoshiyama D, Kuraku S, Katoh K, Kubokawa K, and Miyata T. Protein tyrosine kinase cDNAs from amphioxus, hagfish, and lamprey: isoform duplications around the divergence of cyclostomes and gnathostomes. J Mol Evol. 1999 Nov;49(5):601-8. DOI:10.1007/pl00006581 |
- Robinson DR, Wu YM, and Lin SF. The protein tyrosine kinase family of the human genome. Oncogene. 2000 Nov 20;19(49):5548-57. DOI:10.1038/sj.onc.1203957 |
- Manning G, Whyte DB, Martinez R, Hunter T, and Sudarsanam S. The protein kinase complement of the human genome. Science. 2002 Dec 6;298(5600):1912-34. DOI:10.1126/science.1075762 |
