Disease relevance of Camk2d

• Immunohistochemically, CaM kinase II alpha immunoreactivity was upregulated in the cerebral cortex and hippocampal CA1 area of scrapie-positive mice infected with ME7 scrapie strain [1].
• Unexpectedly, beta(1)AR-induced myocyte hypertrophy and apoptosis are independent of the classic cAMP/PKA pathway, but require activation of Ca(2+)/calmodulin-dependent kinase II (CaMK II) [2].

High impact information on Camk2d

• In RBL-2H3 m1 cells, inhibition of CaM kinase II decreased Thr-1940 phosphorylation, and inhibited release of the secretory granule marker hexosaminidase in response to carbachol but not to antigen [3].
• Similarly, co-transfected Ala --> Thr-1940 human NMHC-IIA was phosphorylated by activated CaM kinase II in HeLa cells, while wild type was not [3].
• Thus, although this study establishes that synapsin I is a substrate for CaM kinase II in the pancreatic beta-cell, this event appears not to be important for the mobilization of insulin granules [4].
• A cDNA clone for the alpha subunit of mouse brain Ca2+/CaM-dependent protein kinase II (CaM-kinase II) was transcribed in vitro and translated in a rabbit reticulocyte lysate system [5].
• These results establish that introduction of negative charge(s) at residue 286, either by autophosphorylation of Thr or by mutation to Asp, is sufficient and necessary to generate the partially Ca2+-independent form of CaM-kinase II [5].

Biological context of Camk2d

• Proteolytic digests of these immunoprecipitates revealed that calcium primarily induced the increased phosphorylation of sites identified as CaM kinase II-specific and distinct from protein kinase A-specific sites [4].
• The stimulation of Ca(2+)-independent (autonomous) CaMK-II enzymatic activity, a barometer of in situ activated CaMK-II, was prevented by the same KN-93 concentrations that cause G1 phase arrest [6].
• These results suggest that D2R is involved in the activation of the nuclear isoform of CaM kinase II and thereby in stimulation of gene expression through Ca(2+) signaling [7].
• Ca+/calmodulin-dependent protein kinase II (CaM kinase II) is regulated by calcium oscillations, autophosphorylation, and its subunit composition [8].
• CaM kinase II is an enzyme that plays a major role in the regulation of long-term potentiation, a form of synaptic plasticity associated with learning and memory [1].

Anatomical context of Camk2d

• To elucidate the cellular function of CaM kinase II, we introduced cDNA of wild-type CaM kinase II alpha- or beta-isoform, and of mutant alpha-isoform (Ala-286 kinase) into two different types of neuroblastoma, Neuro2a (Nb2a) and NG108-15, thus generating cell lines stably producing elevated levels of these kinases [9].
• Some substrates of CaM kinase II related to neurite outgrowth were detected in cells overexpressing the kinase stimulated with H-7 [9].
• Differential autophosphorylation of CaM kinase II from phasic and tonic smooth muscle tissues [8].
• The membrane-permeable cGMP analog 8-bromo-cGMP relaxed gastric fundus smooth muscles and activated CaM kinase II [10].
• Direct inhibition of CaMK-II in 1-day-old neurons immediately froze growth cone dynamics, disorganized F-actin and ultimately led to axon retraction [11].

Associations of Camk2d with chemical compounds

• Serine 416, numbered according to the longest human tau isoform, has been reported to be one of the major phosphorylation sites by CaM kinase II in vitro [12].
• SNP-induced CaM kinase II activation was prevented by KN-93 [10].
• The soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-alpha]quinoxalin-1-one inhibited SNP-induced relaxation and CaM kinase II activation [10].
• Acetylcholine (ACh) increased autonomous CaM kinase II activity in fundus and proximal colon smooth muscles in a time- and dose-dependent manner [8].
• Ryanodine, tetracaine, 2-aminoethoxydiphenylborate, and cyclopiazonic acid inhibited SNP-induced fundus smooth muscle relaxation and CaM kinase II activation [10].

Analytical, diagnostic and therapeutic context of Camk2d

• By immunoprecipitation, in situ phosphorylation of synapsin I was induced in permeabilized betaTC3 cells within a Ca2+ concentration range shown to activate endogenous CaM kinase II under identical conditions [4].
• When soluble CaM kinase II previously autophosphorylated was incubated with PSDs, the kinase was precipitated by centrifugation, indicating that the soluble kinase associated with PSDs and formed a PSD-CaM kinase II complex [13].
• Immunoreactivity of CaM kinase II alpha, measured by Western blot, increased markedly in scrapie-infected brains compared with control brains [1].

References