Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases

Alistair RR Forrest¹ , Darrin F Taylor¹ , Mark L Crowe¹ , Alistair M Chalk¹^,2^,3 , Nic J Waddell¹^,2 , Gabriel Kolle¹ , Geoffrey J Faulkner¹^,2 , Rimantas Kodzius⁴^,6 , Shintaro Katayama⁴ , Christine Wells¹^,5 , Chikatoshi Kai⁴ , Jun Kawai⁴^,6 , Piero Carninci⁴^,6 , Yoshihide Hayashizaki⁴^,6 and Sean M Grimmond¹

¹Institute for Molecular Bioscience and ARC Centre in Bioinformatics, University of Queensland, Brisbane, QLD 4072, Australia

²Queensland Institute for Medical Research, PO Royal Brisbane Hospital, Brisbane, QLD 4029, Australia

³Center for Genomics and Bioinformatics, Karolinska Institutet, S-171 77 Stockholm, Sweden

⁴Genome Exploration Research Group (Genome Network Project Core Group), RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, Yokohama, Kanagawa, 230-0045, Japan

⁵The Eskitis Institute for Cell and Molecular Therapies, Griffith University, QLD 4111, Australia

⁶Genome Science Laboratory, Discovery Research Institute, RIKEN Wako Institute, Wako, Saitama, 351-0198, Japan

author email corresponding author email

Genome Biology 2006, 7:R5doi:10.1186/gb-2006-7-1-r5


Published:	26 January 2006

Subject areas: Genetics, Molecular biology, Bioinformatics

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 webcite.

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.

Conclusion

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.