Disease relevance of CALM2

• Agonist-induced vesicle acidification was blocked by pertussis toxin, inhibitors of phosphatidylinositol-phospholipase C, calmodulin, NO synthase, guanylyl cyclase, or protein kinase G [1].
• Immunohistochemical determination of calcium-calmodulin binding predicts neuronal damage after global ischemia [2].
• Characterization of mutant Bordetella pertussis adenylate cyclase toxins with reduced affinity for calmodulin. Implications for the mechanism of toxin entry into target cells [3].
• Two calmodulin-binding fragments (7.4 kDa and 6.5 kDa) were generated using Staphylococcus aureus V8 protease digestion of synapsin I [4].
• Ovine tracheal ring explants were infected with four different Mycoplasma ovipneumoniae and one M. arginini field isolate and their ability to induce cytopathic effects was tested by measuring ciliary activity and intracellular calmodulin release [5].

High impact information on CALM2

• Known to bind to calmodulin and to enhance microtubule assembly, tau proteins had no cold-stabilizing activity [6].
• The interactions of vascular smooth muscle caldesmon with actin, tropomyosin, and calmodulin were determined under conditions in which the four proteins can form reconstituted Ca2+-sensitive smooth muscle thin filaments [7].
• The mechanism of Ca2+ regulation of vascular smooth muscle thin filaments by caldesmon and calmodulin [7].
• Inhibitors of cAMP-dependent kinase and calcium/calmodulin-dependent kinase did not change the phosphorylation of p37 in the presence of protein kinase C activators. p37 was recovered in a Triton X-100-extractable fraction of this ciliary preparation, suggesting that p37 is membrane associated [8].
• Calmodulin was localized in the small intestine of Necturus maculosa at both the light- and electron-microscopic levels utilizing an affinity-purified, monospecific antibody and immunoperoxidase cytochemistry [9].

Biological context of CALM2

• As calmodulin is essential for cell proliferation, increased CALM2 mRNA levels may reflect an important role for calmodulin in expansion-induced fetal lung growth [10].
• Functional regulation of the cardiac ryanodine receptor by suramin and calmodulin involves multiple binding sites [11].
• Simultaneously, calmodulin localization changes during cell differentiation [12].
• Calmodulin level and cAMP-dependent protein kinase activity of ram germ cells at different stages of spermatogenesis have been determined [12].
• This suggests that various EF hand proteins can substitute for the calmodulin molecule [13].

Anatomical context of CALM2

• Adenylate cyclase (AC) toxin from Bordetella pertussis penetrates eukaryotic cells and upon activation by calmodulin generates unregulated levels of intracellular cAMP [14].
• Localization of calmodulin in the enterocyte of Necturus small intestine [9].
• In round, elongating, and elongated spermatids, calmodulin is closely associated with the developing acrosome; in spermatozoa, it becomes present in the postacrosome, the neck region and the tail [12].
• Properties of a monoclonal antibody directed to the calmodulin-binding domain of rabbit skeletal muscle myosin light chain kinase [15].
• 6. These data suggest that the timing of Ca2+ action on CBF in ovine airway epithelial cells, is unlikely to be determined by phosphorylation reactions involving calmodulin or kinase/phosphatase reactions [16].

Associations of CALM2 with chemical compounds

• In the presence of Ca2+ norchlorpromazine isothiocyanate forms a monocovalent complex with calmodulin: CAPP1-calmodulin (Newton et al, 1983) [17].
• The loss of peptides encompassing residues 38-74 and 127-148, located in the amino and carboxyl halves of calmodulin, respectively, suggests that the hydrophobic rings of CAPP can bind at either one of the two phenothiazine sites [17].
• The methyltransferase that catalyzes the trimethylation of lysine 115 in calmodulin has been purified from sheep brain [18].
• The binding of Ca(2+)- and Ba(2+)-calmodulin to caldesmon and its functional consequence was investigated with three different calmodulin mutants [13].
• 5. While calmodulin inhibitors (calmidazolium and W-7; each n = 5) decreased baseline CBF by an average of 1.1 +/- 0.1 Hz, they did not alter the kinetic relationship between [Ca2+]i and CBF [16].

Physical interactions of CALM2

• Under the conditions of our assay (0.45 microM synapsin I, 4 microM F-actin), half-maximal inhibition of actin binding and bundling by unphosphorylated synapsin I was found with 4.3 and 3.7 microM calmodulin, respectively [19].

Enzymatic interactions of CALM2

• The actin binding activity of synapsin I phosphorylated by cAMP-dependent protein kinase or by calmodulin-dependent protein kinase II showed similar sensitivity to calmodulin inhibition to unphosphorylated synapsin I [19].

Regulatory relationships of CALM2

• Filamin (0.007:actin) also decreased the inhibitory action of caldesmon on actin-activated myosin ATPase and also potentiated the reversal of this inhibition by calmodulin [20].

Other interactions of CALM2

• Estradiol (E(2), 10(-8) mol/L) caused an increase in eNOS activity in plasma membranes in the absence of added calcium, calmodulin, or eNOS cofactors, which was blocked by ICI 182,780 and ERalpha antibody [21].
• Caldesmon inhibited actomyosin with a 10-fold greater potency than calponin in the presence of tropomyosin and inhibition could be reversed by Ca2+ calmodulin under certain conditions [22].
• This suggests that Ca2+ activates calmodulin, which in turn enhances adenylyl cyclase and/or PKA activity to release GH from the sheep pituitary [23].

Analytical, diagnostic and therapeutic context of CALM2

• Using in situ hybridization analysis, we found that the proportion of CALM2-labeled cells increased from 10.3 +/- 1.0% to 21.4 +/- 6.8% by 2 days of TO [10].
• Differential expression of CALM2 was confirmed by Northern blot analysis; CALM2 mRNA levels were increased to 161 +/- 5% of control at 2 days of increased lung expansion, induced by tracheal obstruction (TO), and had returned to control levels at days 4 and 10 [10].
• Using differential display RT-PCR, we isolated a cDNA fragment partially encoding calmodulin 2 (CALM2) and identified the remainder of the coding region by 5'-rapid amplification of cDNA ends [10].
• A competitive ELISA protocol was used to analyze weak cross-reactivity to other calmodulin-binding peptides and proteins [15].
• Complex formation was monitored by high-performance liquid chromatography using a CN reverse-phase column which resolves calmodulin, the calmodulin-norchlorpromazine adduct, and norchlorpromazine isothiocyanate [24].

References