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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAi-dx9gAVNuEoPogvXfRP7UnczWm2t3w23gIrjs8G2BA#_7 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAi-dx9gAVNuEoPogvXfRP7UnczWm2t3w23gIrjs8G2BA#_6 http://www.w3.org/ns/prov#value Calcium is a well established regulator of transcription. Modulation of responses to this ubiquitous second messenger can occur by superposition of coincident Ca2+-independent signals, but there is also growing evidence that the strength, frequency, source, and location of the Ca2+ signal are determinants for specific transcriptional results. These complex variations must be translated into changes in protein function that preserve and process the information conveyed by the original signal. The Ca2+ receptor calmodulin (CaM)1 is involved in many of these changes through its effects on a variety of CaM-binding proteins (1). Among these, the multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) are notable for their effects on components of transcription complexes, directly connecting Ca2+ with changes in gene expression. The highly homologous CaMKI and CaMKIV are distinct from the multimeric CaMKII, although all have broad and overlapping substrate preferences, because their activation is greatly enhanced following phosphorylation catalyzed by \"upstream\" kinases in a manner analogous to the mitogen-activated protein kinase cascade. Based on an evolving understanding of CaMKI/IV regulation and cloning of the CaMKI/IV kinases (CaMKKs), a Ca2+/CaM-dependent protein kinase I/IV cascade (CaMK cascade) has been proposed (2, 3). This review will discuss the biochemical and physiologic basis for the existence of this cascade and its potential for mediating Ca2+ regulation of transcription. Identification and Biochemical Characterization of a CaMK Cascade TOP INTRODUCTION Identification and Biochemical... Does the Cascade Function... Is the Cascade Physiologic? Other Transcriptional Targets... Evidence for a CaMK... REFERENCES CaMKI and CaMKIV are closely related protein kinases with many similarities in mode of activation and substrate preferences in vitro but with different tissue distributions. 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