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

Forrest, Alistair R. R., Taylor, Darrin F., Crowe, Mark L., Chalk, Alistair M., Waddell, Nic J., Kolle, Gabriel, Faulkner, Geoffrey J., Kodzius, Rimantas, Katayama, Shintaro, Wells, Christine, Kai, Chikatoshi, Kawai, Jun, Carninci, Piero, Hayashizaki, Yoshihide and Grimmond, Sean M. (2006) Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases. Genome Biology, 7 1: R5.1-R5.15. doi:10.1186/gb-2006-7-1-r5


Author Forrest, Alistair R. R.
Taylor, Darrin F.
Crowe, Mark L.
Chalk, Alistair M.
Waddell, Nic J.
Kolle, Gabriel
Faulkner, Geoffrey J.
Kodzius, Rimantas
Katayama, Shintaro
Wells, Christine
Kai, Chikatoshi
Kawai, Jun
Carninci, Piero
Hayashizaki, Yoshihide
Grimmond, Sean M.
Title Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
Publication date 2006-01-26
Sub-type Article (original research)
DOI 10.1186/gb-2006-7-1-r5
Open Access Status DOI
Volume 7
Issue 1
Start page R5.1
End page R5.15
Total pages 15
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2006
Language eng
Formatted 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.

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.
© 2006 Forrest et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keyword Biotechnology & Applied Microbiology
Genetics & Heredity
Receptor Tyrosine Kinase
Doublecortin-like Kinase
Messenger-RNA
Splice Variants
Gene-expression
Alternative Promoters
Cell-proliferation
Truncated Receptor
Eph Receptor
C-kit
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 08:47:54 EST