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CALM2  -  calmodulin 2 (phosphorylase kinase, delta)

Ovis aries

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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


Biological context of CALM2


Anatomical context of CALM2


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].


  1. Acidification of serotonin-containing secretory vesicles induced by a plasma membrane calcium receptor. Tamir, H., Liu, K.P., Adlersberg, M., Hsiung, S.C., Gershon, M.D. J. Biol. Chem. (1996) [Pubmed]
  2. Immunohistochemical determination of calcium-calmodulin binding predicts neuronal damage after global ischemia. Picone, C.M., Grotta, J.C., Earls, R., Strong, R., Dedman, J. J. Cereb. Blood Flow Metab. (1989) [Pubmed]
  3. Characterization of mutant Bordetella pertussis adenylate cyclase toxins with reduced affinity for calmodulin. Implications for the mechanism of toxin entry into target cells. Heveker, N., Ladant, D. Eur. J. Biochem. (1997) [Pubmed]
  4. Evidence that two non-overlapping high-affinity calmodulin-binding sites are present in the head region of synapsin I. Goold, R., Baines, A.J. Eur. J. Biochem. (1994) [Pubmed]
  5. Field isolates of Mycoplasma ovipneumoniae exhibit distinct cytopathic effects in ovine tracheal organ cultures. Niang, M., Rosenbusch, R.F., DeBey, M.C., Niyo, Y., Andrews, J.J., Kaeberle, M.L. Zentralblatt für Veterinärmedizin. Reihe A. (1998) [Pubmed]
  6. Purification and characterization of sheep brain cold-stable microtubules. Pirollet, F., Job, D., Fischer, E.H., Margolis, R.L. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  7. The mechanism of Ca2+ regulation of vascular smooth muscle thin filaments by caldesmon and calmodulin. Smith, C.W., Pritchard, K., Marston, S.B. J. Biol. Chem. (1987) [Pubmed]
  8. Protein kinase C-dependent phosphorylation of a ciliary membrane protein and inhibition of ciliary beating. Salathe, M., Pratt, M.M., Wanner, A. J. Cell. Sci. (1993) [Pubmed]
  9. Localization of calmodulin in the enterocyte of Necturus small intestine. Scully, R.R., Dedman, J.R., Schultz, S.G. J. Cell. Sci. (1988) [Pubmed]
  10. Increased expansion of the lung stimulates calmodulin 2 expression in fetal sheep. Gillett, A.M., Wallace, M.J., Gillespie, M.T., Hooper, S.B. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  11. Functional regulation of the cardiac ryanodine receptor by suramin and calmodulin involves multiple binding sites. Hill, A.P., Kingston, O., Sitsapesan, R. Mol. Pharmacol. (2004) [Pubmed]
  12. Evolution of Ca2+- and cAMP-dependent regulatory mechanisms during ram spermatogenesis. Feinberg, J., Pariset, C., Rondard, M., Loir, M., Lanneau, M., Weinman, S., Demaille, J. Dev. Biol. (1983) [Pubmed]
  13. Multiple-sited interaction of caldesmon with Ca(2+)-calmodulin. Huber, P.A., El-Mezgueldi, M., Grabarek, Z., Slatter, D.A., Levine, B.A., Marston, S.B. Biochem. J. (1996) [Pubmed]
  14. Distinct steps in the penetration of adenylate cyclase toxin of Bordetella pertussis into sheep erythrocytes. Translocation of the toxin across the membrane. Rogel, A., Hanski, E. J. Biol. Chem. (1992) [Pubmed]
  15. Properties of a monoclonal antibody directed to the calmodulin-binding domain of rabbit skeletal muscle myosin light chain kinase. Nunnally, M.H., Blumenthal, D.K., Krebs, E.G., Stull, J.T. Biochemistry (1987) [Pubmed]
  16. Mode of Ca2+ action on ciliary beat frequency in single ovine airway epithelial cells. Salathe, M., Bookman, R.J. J. Physiol. (Lond.) (1999) [Pubmed]
  17. Phenothiazine-binding and attachment sites of CAPP1-calmodulin. Newton, D.L., Klee, C.B. Biochemistry (1989) [Pubmed]
  18. Isolation and kinetic characterization of the calmodulin methyltransferase from sheep brain. Han, C.H., Richardson, J., Oh, S.H., Roberts, D.M. Biochemistry (1993) [Pubmed]
  19. Coordinated regulation of synapsin I interaction with F-actin by Ca2+/calmodulin and phosphorylation: inhibition of actin binding and bundling. Goold, R., Chan, K.M., Baines, A.J. Biochemistry (1995) [Pubmed]
  20. Filamin and gelsolin influence Ca(2+)-sensitivity of smooth muscle thin filaments. Gusev, N.B., Pritchard, K., Hodgkinson, J.L., Marston, S.B. J. Muscle Res. Cell. Motil. (1994) [Pubmed]
  21. Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae. Chambliss, K.L., Yuhanna, I.S., Mineo, C., Liu, P., German, Z., Sherman, T.S., Mendelsohn, M.E., Anderson, R.G., Shaul, P.W. Circ. Res. (2000) [Pubmed]
  22. Properties of calponin isolated from sheep aorta thin filaments. Marston, S.B. FEBS Lett. (1991) [Pubmed]
  23. Interaction of cyclic AMP- and calcium-dependent mechanisms in the regulation of growth hormone-releasing hormone-stimulated growth hormone release from ovine pituitary cells. Sartin, J.L., Coleman, E.S., Steele, B. Domest. Anim. Endocrinol. (1996) [Pubmed]
  24. Calcium ion dependent covalent modification of calmodulin with norchlorpromazine isothiocyanate. Newton, D.L., Burke, T.R., Rice, K.C., Klee, C.B. Biochemistry (1983) [Pubmed]
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