CALMODULIN TARGET PROTEINS; STRUCTURE-FUNCTION RELATIONSHIPS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究计划对不同家族的钙调素依赖蛋白进行研究，以确定：（1）钙调素（CAM）的结构或功能结合基序，磷酸化位点或假底物结构域或与CAM结合结构域相关的同源区域的位置;（2）不同真核基因组中EF手蛋白的比较及其信号通路的示踪元件;（3）在数据库中搜索与CAM结合和CAM结合位点附近的二级结构预测相关的区域相似的序列;（4）利用后处理CAM假基因作为进化的中性标记，检验分类群之间的系统发育关系和分歧年龄。结合蛋白质的动态规划程序。研究的蛋白质序列包括CAM靶蛋白的整个谱。频谱包括：1类靶蛋白与CAM结合，但不与钙结合，可能对钙/CAM的亲和力降低; 2类蛋白在无钙时与CAM强烈结合，可能被钙激活; 3类蛋白对钙/CAM具有高亲和力，并被钙激活。1类例子是神经调节素、神经颗粒素和一些IQ基序蛋白。第2类是巨噬细胞NO合酶、肺环状3 ′，5 ′-核苷酸磷酸二酯酶、百日咳杆菌腺苷酸环化酶和糖原磷酸化酶B激酶;第3类含有酶和蛋白质，如钙调磷酸酶、肌球蛋白轻链激酶、钙调蛋白、腺苷酸环化酶、胞衬蛋白、MARCKS蛋白、内收蛋白、蛋白激酶、钙依赖性ATP酶泵等。 出版物- Rhoads，A.R. Friedberg，F.：“用于钙调素识别的序列基序。“：FASEB J. 11：331-340：1997; Rhoads，A.R.，Karkera，J.D.，Detera-Wadleigh，S. D.：“锂敏感Wnt信号通路中基因的辐射杂交作图。《分子精神病学》4：437-442：1999; Friedberg，F. Rhoads，A.R.：“计算和验证逆加工假基因的年龄。《分子系统发生学和进化》，第16期，2000年（出版中）;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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);