The accessory domains lost from these catalytic var tin, PKC PE DAG, pleckstrin homology. The role of variants consisting only of accessory domains is unknown. Alternative forms of the receptor kinases and phosphatases A class of phosphoregulators with multiple reported then exam ples of transcriptionally derived dominant negative products is the receptor kinases. For these loci, multiple soluble secreted and membrane tethered decoy receptors lacking cat alytic domains have been described. We therefore undertook a computational review of transcripts of the 56 tyrosine iants are largely interaction domains 13 potential tethered decoys possessing intact transmembrane and extracellular domains, of which four had been reported previously in the literature.

and 26 potential soluble secreted proteins possessing the lig and binding domain and no transmembrane domain, of which seven had previously been reported. The review of these loci also identified a further two classes Inhibitors,Modulators,Libraries of potential variants. Alternative TSS within loci frequently gen erated transcripts encoding peptides that lacked amino ter minal features. Many Inhibitors,Modulators,Libraries of these variants lacked the signal peptide, whereas others lacked both the signal Inhibitors,Modulators,Libraries pep tide and the transmembrane domain. We refer to these two variant types as TMcatalytic and catalytic, respectively. TMcatalytic forms resemble the type 2 trans membrane phosphoregulators such as the nonreceptor phos phatase Ptpn5, which localizes to the endoplasmic reticulum, and the kinase Nok, which localizes to cytoplasmic puncta. We identified 13 of the TMcatalytic class and 12 of the catalytic class.

We then compiled supporting evidence for expression Inhibitors,Modulators,Libraries of these transcripts in normal mouse tissues. All but two of the secreted and tethered forms are gen erated by alternative 3 ends hence we searched for microarray probes and MPSS signatures diagnostic of these alternative 3 ends. The Mouse Transcriptome Project provides MPSS gene expression data from a panel of 85 tissue samples. Similarly, the GNF gene atlas provides gene expression data using Affymetrix arrays for a panel Inhibitors,Modulators,Libraries of 61 normal mouse tissues. The Mouse Transcriptome Project provided support for nine of the secreted proteins, four tethered decoys, and one cytoplas mic catalytic form. The GNF gene atlas provided TKI-258 support for an additional four secreted and one tethered form. MPSS also provided evidence for tissue specific expression of nine novel isoforms seven secreted forms, one tethered form of Axl in kidney. and one catalytic form of Ptprg in brain, kidney, white fat, and car tilage. Similarly, the GNF gene atlas provided evidence for tis sue specific expression of two novel secreted isoforms Ptprk in blastocysts and Ptprg in brain.