Disease relevance of Camk2b

• The activity and levels of CaM kinase II-alpha was investigated in the cytosolic and membrane fraction of mice cerebral cortex and cerebellum using an experimental model of fatal murine cerebral malaria (FMCM) [1].
• We reported evidence for CaM kinase II and a synapsin I-like protein present in mouse insulinoma MIN6 cells (Matsumoto, K., Fukunaga, K., Miyazaki, J., Shichiri, M., and Miyamoto, E. (1995) Endocrinology 136, 3784-3793) [2].
• Previous studies utilizing crude brain homogenates have shown that forebrain ischemia results in inhibition of calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity without large-scale proteolysis of the enzyme [3].
• Since the expression of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) is regulated during brain development, the developmental change of the enzyme was investigated during the neural differentiation of murine P19 embryonal carcinoma cells [4].
• Treating the mouse intestine with the calmodulin antagonist W-7 and KN-93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase II (CaMK II), reduced the sensitivity of the host to the action of Escherichia coli heat-stable enterotoxin II (STII) [5].

High impact information on Camk2b

• To relate different forms of synaptic plasticity to the formation and maintenance of place cells in the hippocampus, we have recorded place cells in freely behaving, transgenic mice that express a mutated Ca2+-independent form of CaM Kinase II [6].
• We have examined glutamate receptors (GluRs) as substrates for CaM-K II because (1) they are colocalized in the PSD, (2) cloned GluRs contain consensus phosphorylation sites for protein kinases including CaM-K II, and (3) several GluRs are regulated by other protein kinases [7].
• We report here that CaM-K II phosphorylates GluR in several in vitro systems, including the PSD, and that activated CaM-K II enhances kainate-induced ion current three- to fourfold in cultured hippocampal neurons [7].
• Regulation of GluRs, which are involved in excitatory synaptic transmission and in mechanisms of learning and memory, by CaM-K II is of interest because of the postulated role of CaM-K II in synaptic plasticity and its known involvement in induction of long-term potentiation [7].
• In this issue of Neuron, Yasuda and Mayford report an elegant cell-type restricted inducible transgenic mouse overexpressing a mutant form of CaM kinase II selectively in superficial layers of medial entorhinal cortex and its upstream regions [8].

Biological context of Camk2b

• Forty-one affected F(2) and 120 BC(1) segregants from the outcross of GP/Bc to CBA/J, and 23 affected F(2) segregants from the outcross to ICR/Bc, were used to map gp to proximal Chr 11 between the centromere and D11Dal1 (Camk2b), an interval previously defined as less than 1 cM [9].
• These correlative observations caused us to test whether activation of CaM kinase II mediated the chromosomal transit into an anaphase configuration [10].
• CaM kinase II-alpha activity, levels and Ca/calmodulin dependent phosphorylation of substrate proteins in mice brain during fatal murine cerebral malaria [1].
• CaM kinase II constitutes a family of multifunctional protein kinases that play a major role in Ca2+-mediated signal transduction [11].
• The beta-subunit of calmodulin kinase II (beta-CaMK II) is a good candidate for the wr mutation because of its chromosomal localization and tissue distribution [12].

Anatomical context of Camk2b

• CaM kinase II appears localized on midzone microtubules as soon as they form and may have a role in specifying the position of the contractile ring of the second polar body [10].
• These data suggest that CaM kinase II dephosphorylation and deactivation in the pancreatic beta-cell is mediated by the combined action of an okadaic-acid-sensitive phosphatase and a Mg2+-dependent phosphatase, such as PP-2C [13].
• These data show for the first time that Ca/CaMK II activation plays an important role in the transmission of GnRH signals from the plasma membrane to the LH subunit genes [14].
• Additionally, we describe the murine betaM-CaM kinase II, a variant of the 'brain-specific' beta-CaM kinase II, which is highly expressed in skeletal muscle [11].
• Pathology of FMCM resulted in decreased CaM kinase-II activity in both cortex and cerebellum though western analysis revealed no appreciable changes in the levels of CaM kinase-II alpha in cytosol and membrane fractions from control and cerebral malaria infected brain [1].

Associations of Camk2b with chemical compounds

• Blocking calcium influx with nimodipine or depleting intracellular calcium storage pools with thapsigargin each resulted in a partial suppression of GnRH-induced activation of Ca/CaMK II, and in combination, completely suppressed the Ca/CaMK II response to GnRH [14].
• The calcium channel activator Bay K 8644 stimulated a 3-fold increase in Ca/CaMK II activity, similar to GnRH [14].
• Under these conditions, CaM kinase II phosphatase was more sensitive to calyculin A relative to okadaic acid, characteristic of the involvement of PP-1 [13].
• CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels [15].
• Quantitative determination of CaMK II isoform mRNA was carried out in several tissues and beta cells purified by fluorescence activated cell sorting and compared to the housekeeping enzyme pyruvate dehydrogenase [16].

Enzymatic interactions of Camk2b

• Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) is present in a membrane-bound form that phosphorylates synapsin I on neuronal synaptic vesicles and the ryanodine receptor at skeletal muscle sarcoplasmic reticulum (SR), but it is unclear how this soluble enzyme is targeted to membranes [17].

Regulatory relationships of Camk2b

• We suggest that CaM kinase II regulates insulin secretion via phosphorylation of synapsin I-like protein [18].

Other interactions of Camk2b

• We investigated the potential of GnRH acting through calcium to activate calcium/calmodulin-dependent protein kinase type II (Ca/CaMK II) in mouse gonadotrope-derived LbetaT2 cells [14].
• Alpha and beta isoforms of Ca2+/calmodulin-dependent protein kinase II (alpha and beta CaM kinase II, respectively) are highly conserved except for beta-specific insertions 1 and 2, located at amino acids 316-340 and 354-392, respectively [19].
• By analogy concerning regulation of neurotransmitter release, our results suggest that phosphorylation of synapsin I by CaM kinase II may induce the release of insulin from islet cells [2].
• CaM kinase II and phospholamban contribute to caffeine-induced relaxation of murine gastric fundus smooth muscle [20].
• Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals [21].

Analytical, diagnostic and therapeutic context of Camk2b

• GnRH stimulated Ca/CaMK II beta subunit activity 3-fold 2 min after treatment and returned to control values by 45 min [14].
• Indirect immunofluorescence using a monoclonal antibody specific to the CaM kinase II alpha isoform revealed that CaM kinase II was mainly localized in the perikaryal and dendritic cytoplasm of the alpha and Ala-286 transfectants [22].
• Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans [16].
• The expression of CaM kinase II alpha was confirmed by northern blot and immunoblot analyses [23].
• Next we examined the possible coexistence of CaM kinase II alpha isoform and glutamate or that of CaM kinase II beta isoform and glutamic acid decarboxylase (GAD) in the single neuron by double immunofluorescence labelling using a pair of anti-alpha and anti-glutamate antibodies, or a pair of anti-beta and anti-GAD antibodies [24].

References