This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator. The research plan involves examining the different families of calmodulin-dependent proteins to determine: (1) structural or functional binding motifs of calmodulin(CAM) and the position of phosphorylation sites or pseudosubstrate domains or homologous regions relative to the CAM-binding domain; (2) comparison of EF-hand proteins in different eucaryotic genomes and tracing elements of their signaling pathways; (3) searching the database for sequences similar to regions associated with CAM binding and secondary structure prediction in the vicinity of the CAM-binding site; (4) examining the phylogenetic relationships and ages of divergence among taxa utilizing retroprocessed CAM pseudogenes as neutral markers of evolution (5) examination of local multiple alignments of CAM-binding proteins by dynamic programming procedures. Protein sequences investigated include the entire spectrum of CAM target proteins. The spectrum includes: Class 1 target proteins that bind to CAM without associated calcium and may have reduced affinity for calcium/CAM; Class 2 proteins that bind CAM strongly in the absence of calcium and may be positively activated by calcium; and the major Class 3 proteins that have high affinity for the calcium/CAM and are activated by it. Class 1 examples are neuromodulin, neurogranin and some IQ motif proteins. Class 2 are macrophage NO synthase, lung cyclic 3`, 5`-nucleotide phosphodiesterase, bordetella pertussis adenylate cyclase, and glycogen phosphorylase b kinase;and class 3 containing the enzymes and proteins such as calcineurin, myosin light chain kinase, caldesmon, adenylate cyclases, fodrin, MARCKS protein, adducins, protein kinases, calcium-dependent ATPase pumps and others. Publications - Rhoads, A.R. and Friedberg, F.: 'Sequence Motifs for Calmodulin Recognition.': FASEB J. 11: 331-340: 1997; Rhoads, A.R., Karkera, J.D., and Detera-Wadleigh, S.D.: 'Radiation Hybrid Mapping of Genes in the Lithium-Sensitive Wnt Signaling Pathway.' : Molecular Psychiatry 4: 437-442: 1999; Friedberg, F. and Rhoads, A.R.: 'Calculation and Verification of the Ages of Retroprocessed Pseudogenes.': Molecular Phylogenetics and Evolution: 16: 2000 (In Press);
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