title: Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases.
abstract: BACKGROUND
  Alternative transcripts of protein kinases and protein phosphatases are known to encode peptides with altered substrate affinities, subcellular localizations, and activities. We undertook a systematic study to catalog the variant transcripts of every protein kinase-like and phosphatase-like locus of mouse http://variant.imb.uq.edu.au.
  
  
  RESULTS
  By reviewing all available transcript evidence, we found that at least 75% of kinase and phosphatase loci in mouse generate alternative splice forms, and that 44% of these loci have well supported alternative 5' exons. In a further analysis of full-length cDNAs, we identified 69% of loci as generating more than one peptide isoform. The 1,469 peptide isoforms generated from these loci correspond to 1,080 unique Interpro domain combinations, many of which lack catalytic or interaction domains. We also report on the existence of likely dominant negative forms for many of the receptor kinases and phosphatases, including some 26 secreted decoys (seven known and 19 novel: Alk, Csf1r, Egfr, Epha1, 3, 5,7 and 10, Ephb1, Flt1, Flt3, Insr, Insrr, Kdr, Met, Ptk7, Ptprc, Ptprd, Ptprg, Ptprl, Ptprn, Ptprn2, Ptpro, Ptprr, Ptprs, and Ptprz1) and 13 transmembrane forms (four known and nine novel: Axl, Bmpr1a, Csf1r, Epha4, 5, 6 and 7, Ntrk2, Ntrk3, Pdgfra, Ptprk, Ptprm, Ptpru). Finally, by mining public gene expression data (MPSS and microarrays), we confirmed tissue-specific expression of ten of the novel isoforms.
  
  
  CONCLUSIONS
  These findings suggest that alternative transcripts of protein kinases and phosphatases are produced that encode different domain structures, and that these variants are likely to play important roles in phosphorylation-dependent signaling pathways.
authors.affiliation: Institute for Molecular Bioscience and ARC Centre in Bioinformatics, University of Queensland, Brisbane, QLD 4072, Australia. a.forrest@imb.uq.edu.au
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.forename: Darrin F
authors.initials: DF
authors.lastname: Taylor
authors.forename: Mark L
authors.initials: ML
authors.lastname: Crowe
authors.forename: Alistair M
authors.initials: AM
authors.lastname: Chalk
authors.forename: Nic J
authors.initials: NJ
authors.lastname: Waddell
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kolle
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Faulkner
authors.forename: Rimantas
authors.initials: R
authors.lastname: Kodzius
authors.forename: Shintaro
authors.initials: S
authors.lastname: Katayama
authors.forename: Christine
authors.initials: C
authors.lastname: Wells
authors.forename: Chikatoshi
authors.initials: C
authors.lastname: Kai
authors.forename: Jun
authors.initials: J
authors.lastname: Kawai
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002384:Catalysis; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D016678:Genome / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010455:Peptides / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020033:Protein Isoforms; D011494:Protein Kinases / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D010455:Peptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases