Disease relevance of CALM1

• When Ba2+ (which does not interact with calmodulin) is substituted for Ca2+, the control KCl-evoked release of each transmitter is unaffected and tetanus toxin is still inhibitory [1].
• Vimentin rearrangement during African swine fever virus infection involves retrograde transport along microtubules and phosphorylation of vimentin by calcium calmodulin kinase II [2].
• While vertebrate calmodulin binds 4.2 +/- 0.2 equiv of TFP, Escherichia coli expressed but unmutated calmodulins bind about 5.0 +/- 0.5 equiv of TFP [3].
• Calmodulin activities are significantly increased in both uninvolved and involved epidermis in psoriasis [4].
• Ca(2+) current and caffeine contractures were not affected by calmodulin [5].

High impact information on CALM1

• The deduced primary structure of this DGK contains the putative ATP-binding sites, two cysteine-rich zinc finger-like sequences similar to those found in protein kinase C, and two E-F hand motifs, typical of Ca2(+)-binding proteins like calmodulin [6].
• Phosphorylation of tubulin with a calmodulin-dependent protein kinase similar to that found in postsynaptic densities inhibits its ability to self-assemble into microtubules in a reversible fashion [7].
• In smooth muscle, cyclic attachment and detachment of cross-bridges is thought to be induced by a Ca2+- and calmodulin-dependent myosin light chain kinase which phosphorylates myosin [8].
• The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and the naphthalene sulfonamides, W-7 and W-13 (10(-5) M), inhibited gastrin-stimulated HIP by 45.6 38.5, 42.3, and 37.2%, respectively [9].
• Calmodulin at 0.5-10 micrograms/ml stimulated the Ca pumping activity of EGTA-washed podosomes [10].

Chemical compound and disease context of CALM1

• Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation [11].

Biological context of CALM1

• This structural element is also known for a calmodulin binding protein [12].
• Axonal transport of calmodulin: a physiologic approach to identification of long-term associations between proteins [13].
• Submaximal Ca2+ contractions can be reversibly depressed by preincubation of relaxed fibers with cPK catalytic subunit (300 U/ml), even in the presence of 4 micro M CaM [14].
• The calmodulin inhibitors trifluoperazine and pimozide (30 microM) blocked the cell motility induced by ionomycin while they left the increase of intracellular calcium unaffected [15].
• Troponin C displaces the half-maximal concentration for activation by Ca2+ to pCa 5.46 and the cooperativity between the Ca2+ binding sites to nH 1.1, compared with pCa 6.14 and nH 1.72 when calmodulin is used [16].

Anatomical context of CALM1

• Here we determine the role of CaM Met residues in the productive association of CaM with RyR2, as assessed via determinations of [3H]ryanodine and [35S]CaM binding to cardiac muscle sarcoplasmic reticulum (SR) vesicles [17].
• Although histamine does not require extracellular or membrane calcium events to stimulate the oxyntic cell, calmodulin appears to participate in histamine action [18].
• Calmodulin moves in axonal transport independent of the movements of microtubules (SCa) and membranes (FC), which suggests that the interactions of calmodulin with these structures may represent a transient interaction between groups of proteins moving in axonal transport at different rates [13].
• In the particulate subfractions enriched in nuclei, mitochondria, microsome, or plasma membrane, no substrates for the phospholipid-sensitive enzyme were demonstrated but at least four substrates for the calmodulin-sensitive enzyme were identified [19].
• In contrast, after the acrosome reaction, although other features of calmodulin distribution remained the same, the fluorescence associated with the anterior half of the head was notably absent [20].

Associations of CALM1 with chemical compounds

• Role of calmodulin methionine residues in mediating productive association with cardiac ryanodine receptors [17].
• In contrast, replacing the NH2-terminal Met of CaM with Leu increased the concentration of CaM required to inhibit CSR [3H]ryanodine binding but did not alter the extent of inhibition [17].
• The action of carbamylcholine is completely dependent upon calcium/calmodulin mediation, supporting the concept that cholinergic actions are mediated via calcium-calmodulin events [18].
• The calmodulin antagonists, trifluoperazine (10(-5) M), pimozide (10(-5) M), and a naphthalenesulfonamide (W-7), inhibited the integrated response to histamine by 54, 56, and 53%, and that of carbamylcholine by 65, 64, and 99%, respectively [18].
• [Ca2+]i chelator and calmodulin antagonist inhibited the carbachol-induced pepsinogen secretion and NO generation [21].

Physical interactions of CALM1

• Missense mutation analysis indicates that the Lys and Arg residues are essential for calmodulin binding to the synthetic peptide RYR1 PM3 [22].
• Amino-terminal conserved region in proteinase inhibitor domain of calpastatin potentiates its calpain inhibitory activity by interacting with calmodulin-like domain of the proteinase [23].
• The temperature dependence of glucagon binding by calmodulin shows that the association is enthalpy driven [24].
• The stoichiometry of calmodulin binding to MBP was approximately 1:1 [25].

Enzymatic interactions of CALM1

• In skeletal muscle SR, however, the level of cAMP-PK or calmodulin catalyzed phosphorylation of the intact ryanodine receptor (0.2 or 2.9 pmol Pi/mg SR, respectively) was much less than the [3H]ryanodine binding activity of this fraction (11.6 pmol/mg) [26].

Regulatory relationships of CALM1

• Furthermore, a mutant CaM deficient in Ca2+ binding at all four Ca2+ sites significantly activated the RYR2 and acted as a competitive inhibitor of RYR2 regulation by wild-type Ca2+CaM [27].
• Benzylisoquinoline compounds inhibit the ability of calmodulin to activate cyclic nucleotide phosphodiesterase [28].
• The calmodulin-dependent block of MARCKS phosphorylation was observed only in acoustic nerve. p12 shares several characteristics with myelin basic protein (MBP) [29].

Other interactions of CALM1

• Regulation of the RYR1 and RYR2 Ca2+ release channel isoforms by Ca2+-insensitive mutants of calmodulin [27].
• In submicromolar Ca2+, activation of the RYR1 isoform by each of the single-point CaM mutants was similar to that by wild-type apoCaM, whereas in micromolar Ca2+, RYR1 inhibition by Ca2+CaM was abolished by mutations targeting CaM's C-terminal Ca2+ sites [27].
• (6) The phosphotransferase activity of the purified CaMKII was in vitro inhibited after transphosphorylation by PKC if calmodulin was absent during transphosphorylation [30].
• Thus, it appears that Ca2+-binding site I of calmodulin is at or near binding sites of calmodulin for TnI, TnT, and phospholamban [31].
• Ca2+ potentiates cAMP-dependent expression of urokinase-type plasminogen activator gene through a calmodulin- and protein kinase C-independent mechanism [32].

Analytical, diagnostic and therapeutic context of CALM1

• Co-electrophoresis of purified calmodulin and radioactively labeled SCb proteins in two dimensional polyacrylamide gel electrophoresis (PAGE) demonstrated the identity of the heat-stable SCb protein and calmodulin on the basis of pI, molecular weight, and anomalous migration in the presence of Ca2+-chelating agents [13].
• The location of calmodulin in rabbit and guinea pig spermatozoa was determined by indirect immunofluorescence techniques [20].
• Spermatozoa that had not undergone the acrosome reaction exhibited four distinct regions of calmodulin-specific immunofluorescence: around the acrosome, in a band across the lower third of the head, and in two localized areas at the base and tip of the flagellum [20].
• This antiserum (rabbit anti-calmodulin serum) also detects 4-15 times less calmodulin immunoreactivity than sheep anti-calmodulin antibody by radioimmunoassay of vesicles solubilized with nondenaturing detergents [33].
• Reassociation of calmodulin with its target enzyme was weak since all calmodulin remained in the supernatant after a single centrifugation [34].

References