Open Access Highly Accessed Open Badges Research

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

Alistair RR Forrest1*, Darrin F Taylor1, Mark L Crowe1, Alistair M Chalk123, Nic J Waddell12, Gabriel Kolle1, Geoffrey J Faulkner12, Rimantas Kodzius46, Shintaro Katayama4, Christine Wells15, Chikatoshi Kai4, Jun Kawai46, Piero Carninci46, Yoshihide Hayashizaki46 and Sean M Grimmond1

Author Affiliations

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

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

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

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

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

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

For all author emails, please log on.

Genome Biology 2006, 7:R5  doi:10.1186/gb-2006-7-1-r5

Published: 26 January 2006



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 webcite.


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.


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.