and the protein phosphatases, which remove them. Reports of alternative isoforms selleck kinase inhibitor of Inhibitors,Modulators,Libraries these pro teins are common and for some loci such as HGK, which con tains nine reported alternatively spliced modules, the number of variants themselves is impressive. For these enzymes variants that alter or remove the catalytic domain are known to affect activity and substrate specificity. In others, such as the fibroblast growth factor receptors Fgfr1 and 2, restricted expression of splice variants with altered ligand binding domains allow cells to elicit tissue specific responses. To examine the impact of alternative transcripts on this sys tem we undertook a systematic study of the variant tran scripts of mouse protein kinase and protein phosphatase loci. we refer to these collectively as the phosphoregulators.

To do this we Inhibitors,Modulators,Libraries exploited the wealth of mouse full length cDNA sequences generated by the Functional Annotation of Mouse 3 project and all available Inhibitors,Modulators,Libraries public mouse cDNA sequences. We report on the frequency of alternative forms, domain content, and the levels of support for each iso form, and we speculate on the role these isoforms are likely to play Inhibitors,Modulators,Libraries in the regulation of protein phosphorylation. Results The kinase like and phosphatase like loci of mouse Before attempting to catalogue the alternative transcripts of mouse protein kinase like and phosphatase like loci of mouse, we first reviewed all putative kinases and phos phatases identified in the literature and combined the results with new sequences identified by InterProScan predictions of open reading frames from the FANTOM3, GenBank, and Refseq databases.

In 2003 we estimated that there are 561 kinase like genes in mouse, using the domain predictor InterProScan to iden tify sequences containing kinase like motifs in all available cDNA sequences and all ENSEMBL gene predictions. In 2004 an alternative estimate Inhibitors,Modulators,Libraries of 540 kinase like genes was reported. We undertook a systematic review of both data sets and now revise the estimate down to 527 kinase like loci, and there is transcriptional evidence for 522 of these. We removed all false positives introduced by the ProSite kinase domain motif, and duplicates introduced by par tial ENSEMBL gene predictions. Similarly, for the phos phatase like loci of mouse we revised the estimate to 160 loci, and there is transcriptional evidence for 158 of these. first We sum marize the evidence for each locus in Additional data file 1. The FANTOM3 data set identified three new kinase like loci. These are I0C0018M10, Gm655, and a second transcriptionally active copy of the TP53 regulating kinase. The kinase like loci I0C0018M10 and Gm655 appear to represent transcriptionally active pseudo genes with truncated kinase domains.