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)

Multifunctional Ca(2+)-calmodulin-dependent protein kinase (CaMKII) is a Ser/Thr protein kinase uniformly distributed within the sarcoplasmic reticulum (SR) of skeletal muscle. In fast twitch muscle, no specific substrates of CaMKII have yet been identified in nonjunctional SR. Previous electron microscopy data showed that glycogen particles containing glycogen synthase (GS) associate with SR at the I band level. Furthermore, recent evidence implicates CaMKII in regulation of glucose and glycogen metabolism. Here, we demonstrate that the glycogen- and protein phosphatase 1-targeting subunit, also known as G(M), selectively localizes to the SR membranes of rabbit skeletal muscle and that G(M) and GS co-localize at the level of the I band. We further show that G(M), GS, and PP1c assemble in a structural complex that selectively localizes to nonjunctional SR and that G(M) is phosphorylated by SR-bound CaMKII and dephosphorylated by PP1c. On the other hand, no evidence for a structural interaction between G(M) and CaMKII was obtained. Using His-tagged G(M) recombinant fragments and site-directed mutagenesis, we demonstrate that the target of CaMKII is Ser(48). Taken together, these data suggest that SR-bound CaMKII participates in the regulation of GS activity through changes in the phosphorylation state of G(M). Based on these findings, we propose that SR-bound CaMKII participates in the regulation of glycogen metabolism, under physiological conditions involving repetitive raises elevations of [Ca(2+)](i).
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PMID:Glycogen- and PP1c-targeting subunit GM is phosphorylated at Ser48 by sarcoplasmic reticulum-bound Ca2+-calmodulin protein kinase in rabbit fast twitch skeletal muscle. 1559 18

Ca(2+)/calmodulin-dependent protein kinase (CaMK) IV is a multifunctional Ser/Thr protein kinase that is predominantly expressed in the nuclei of neurons. CaMKIV consists of a catalytic domain and a regulatory (Ca(2+)/calmodulin binding and autoinhibitory) domain, which are located in the N-terminal and central regions, respectively. Here, we identified the zebrafish homologue of CaMKIV (zCaMKIV) on the basis of biochemical characterization. zCaMKIV showed similar biochemical properties as well as tissue and subcellular distributions to rat CaMKIV (rCaMKIV). However, zCaMKIV had a fairly small size with a molecular mass of about 40 kDa, and was devoid of a region corresponding to the C-terminal domain of rCaMKIV. Since zCaMKIV is composed of regions that are nearly equivalent to only a catalytic and a regulatory domain, it should represent a minimum size homologue possessing CaMKIV function. zCaMKIV and rCaMKIV differed in their substrate specificities, since rCaMKIV preferred histone H1 over myelin basic protein, while zCaMKIV did not. Moreover, zCaMKIV was more readily dephosphorylated by zebrafish nuclear CaMK phosphatase (CaMKP-N) than rCaMKIV. These results suggest that the C-terminal region of CaMKIV plays a role in interacting with its target and modulator proteins.
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PMID:A minimum size homologue of Ca2+/calmodulin-dependent protein kinase IV naturally occurring in zebrafish. 2019 Feb 69