Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A transgenic mouse insertional mutant displayed the phenotype of altered cranial morphology with sex-linked cleft palate. We have cloned the disrupted genomic X-linked locus and report the identification of the mCASK gene. The gene is transcribed to produce two messages of 4.5 and 9.5 kb expressed during development and in adult tissues, particularly the brain. We describe the isolation of two differentially spliced mouse cDNAs from the locus (mCASK-A and mCASK-B). The mCASK-B cDNA probably represents the full-length product of the 4.5-kb transcript. The identical N-termini of the predicted encoded proteins (mCASK-A and -B) are highly homologous to Ca2+/calmodulin-dependent protein kinase II, while the deduced C-terminus of mCASK-B is highly homologous to a family of multidomain proteins containing a guanylate kinase motif, the MAGUK proteins. mCASK-B is a new member of an emerging family of genes in which the encoded proteins combine these domains, termed here, the CAMGUKs, including rat CASK, Caenorhabditis elegans lin-2, and Drosophila caki/camguk. The CAMGUKs are likely to be effectors in signal transduction as regulatory partners of transmembrane molecules, modulated by calcium and nucleotides. The transgene in this mutant mouse line integrated into an intron that bisects the encoded calmodulin-binding domain, a potentially important regulatory domain of the predicted protein, generating hybrid transcripts.
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PMID:Murine CASK is disrupted in a sex-linked cleft palate mouse mutant. 978 75

Synapse-associated protein 97 (SAP97), a member of membrane-associated guanylate kinase protein family, has been implicated in the processes of targeting ionotropic glutamate receptors at postsynaptic sites. Here we show that SAP97 is enriched at the postsynaptic density where it co-localizes with both ionotropic glutamate receptors and downstream signaling proteins such as Ca2+/calmodulin-dependent protein kinase II (CaMKII). SAP97 and alphaCaMKII display a high co-localization pattern in hippocampal neurons as well as in transfected COS-7 cells. Metabolic labeling of hippocampal cultures reveals that N-methyl-D-aspartic acid (NMDA) receptor activation induces CaMKII-dependent phosphorylation of SAP97; co-incubation with the CaMKII-specific inhibitor KN-93 reduces SAP97 phosphorylation to basal levels. Our results show that SAP97 directly interacts with the NR2A subunit of NMDA receptor both in an in vitro "pull-out" assay and in co-immunoprecipitation experiments from homogenates and synaptosomes purified from hippocampal rat tissue. Interestingly, in the postsynaptic density fraction, SAP97 fails to co-precipitate with NR2A. We show here that SAP97 is directly associated with NR2A through its PDZ1 domain, and CaMKII-dependent phosphorylation of SAP97-Ser-232 disrupts NR2A interaction both in an in vitro pull-out assay and in transfected COS-7 cells. Moreover, expression of SAP97(S232D) mutant has effects similar to those observed upon constitutively activating CaMKII. Our findings suggest that SAP97/NR2A interaction is regulated by CaMKII-dependent phosphorylation and provide a novel mechanism for the regulation of synaptic targeting of NMDA receptor subunits.
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PMID:CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction. 1293 8