Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases.
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.
Forrest
Alistair R R
AR
Institute for Molecular Bioscience and ARC Centre in Bioinformatics, University of Queensland, Brisbane, QLD 4072, Australia. a.forrest@imb.uq.edu.au
Taylor
Darrin F
DF
Crowe
Mark L
ML
Chalk
Alistair M
AM
Waddell
Nic J
NJ
Kolle
Gabriel
G
Faulkner
Geoffrey J
GJ
Kodzius
Rimantas
R
Katayama
Shintaro
S
Wells
Christine
C
Kai
Chikatoshi
C
Kawai
Jun
J
Carninci
Piero
P
Hayashizaki
Yoshihide
Y
Grimmond
Sean M
SM
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*
D018076:DNA, Complementary; D010455:Peptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases