Alternative Splicing Produces Transcripts Encoding Four Variants of Mouse G-Protein-Coupled Receptor Kinase 6
Copyright policy )Alternative Splicing Produces Transcripts Encoding Four Variants of Mouse G-Protein-Coupled Receptor Kinase 6
A family of protein kinases, termed G-protein-coupled receptor kinases (GRK1-6), is known to phosphorylate agonist-occupied G-protein-coupled receptors. We have identified mRNAs encoding four distinct mouse GRK6 isoforms (mGRK6), designated mGRK6-A through mGRK6-D. Mouse GRK6-B and mGRK6-C diverge from the known human GRK6 (577 residues) at residue 560 and are 13 residues longer and 16 residues shorter, respectively, than human GRK6, while mGRK6-A very likely represents the mouse equivalent of human GRK6. Mouse GRK6-D is identical to the other mGRK6 variants in the amino-terminal region, but comprises only 59 of the 263 amino acids of the putative catalytical domain. As mGRK6-D retains the region involved in interacting with activated receptors, but most likely lacks catalytic activity, this variant might represent a naturally occurring inhibitor of other GRKs. Analysis of the genomic organization of mGRK6 gene revealed that the four mRNAs are generated by alternative RNA splicing from a single approximately 14. 5-kb gene, made up of at least 17 exons and located on mouse chromosome 13. Similar to human GRK6, mGRK6-A contains three cysteine residues within its carboxyl-terminal region known to serve as substrates for palmitoylation. Mouse GRK6-B lacks these palmitoylation sites, but carries a basic carboxyl-terminus containing consensus sequences for phosphorylation by protein kinases C and cAMP/cGMP-dependent protein kinases. Mouse GRK6-C displays none of these motifs. Thus, mGRK6-A, mGRK6-B, and mGRK6-C are predicted to differ in terms of their regulation by carboxyl-terminal posttranslational modification. Analysis of mRNA expression revealed that the four mGRK6 mRNAs are differentially expressed in mouse tissues, suggesting that the four mGRK6 isoforms are involved in regulating tissue- or cell type-specific functions in vivo.
- University of Ulm Germany
Base Sequence, Models, Genetic, Sequence Homology, Amino Acid, Molecular Sequence Data, Genetic Variation, Exons, Protein Serine-Threonine Kinases, G-Protein-Coupled Receptor Kinases, Gene Expression Regulation, Enzymologic, Mice, Inbred C57BL, Alternative Splicing, Mice, Species Specificity, Mice, Inbred CBA, Animals, Humans, Amino Acid Sequence, RNA, Messenger, In Situ Hybridization, Fluorescence, DNA Primers
Base Sequence, Models, Genetic, Sequence Homology, Amino Acid, Molecular Sequence Data, Genetic Variation, Exons, Protein Serine-Threonine Kinases, G-Protein-Coupled Receptor Kinases, Gene Expression Regulation, Enzymologic, Mice, Inbred C57BL, Alternative Splicing, Mice, Species Specificity, Mice, Inbred CBA, Animals, Humans, Amino Acid Sequence, RNA, Messenger, In Situ Hybridization, Fluorescence, DNA Primers
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