Sandbox Reserved 970: Difference between revisions

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== Regulations ==

There are different kind of calcium ATPase regulations. For example, the phospholamban (PLN or PLB) is a membrane protein that regulates the calcium pump in cardiac muscle and skeletal muscle cells. This small phosphoprotein is a pentamer. The phospholamban can be phosphorylated at three distinct sites by various protein kinases (PKA, PKC, CamK...). The phosphorylation state is ~~mediatedthrough~~ beta-adrenergic stimulation. In unphosphorylate state, the phospholamban inhibits the activity of calcium pump in cardiac and skeletal muscle cells by decreasing the apparent affinity of the ATPase for calcium. The phosphorylation of the protein results in the dissociation of the protein from the ATPase. The phosphoprotein binds just downstream of the active ATPase site (asp351).

There are different kind of calcium ATPase regulations. For example, the phospholamban (PLN or PLB) is a membrane protein that regulates the calcium pump in cardiac muscle and skeletal muscle cells. This small phosphoprotein is a pentamer. The phospholamban can be phosphorylated at three distinct sites by various protein kinases (PKA, PKC, CamK...). The phosphorylation state is mediated through beta-adrenergic stimulation. In unphosphorylate state, the phospholamban inhibits the activity of calcium pump in cardiac and skeletal muscle cells by decreasing the apparent affinity of the ATPase for calcium. The phosphorylation of the protein results in the dissociation of the protein from the ATPase. The phosphoprotein binds just downstream of the active ATPase site (asp351).

~~The activity of the calcium pump is also regulated by by calmodulin, acidic phospholipids and phosphorylation by kinases A and C.~~ Most of the activation mechanisms implicate the C-terminal region of the pump containing the high affinity calmodulin binding domain, which is involved in the autoinhibition of the pump<ref>Marianela G.Dalghi, Marisa M.Fernández, Mariela Ferreira-Gomes, Irene C.Mangialavori, Emilio L.Malchiodi, Emanuel E.Strehler and Juan Pablo F.C.Rossi, 2013 - ''Plasma Membrane Calcium ATPase Activity Is Regulated by Actin Oligomers through Direct Interaction'' - The Journal of Biological Chemistry, p.288, 23380-23393, http://www.jbc.org/content/288/32/23380.full.</ref>.

Most of the activation mechanisms implicate the C-terminal region of the pump containing the high affinity calmodulin binding domain, which is involved in the autoinhibition of the pump<ref>Marianela G.Dalghi, Marisa M.Fernández, Mariela Ferreira-Gomes, Irene C.Mangialavori, Emilio L.Malchiodi, Emanuel E.Strehler and Juan Pablo F.C.Rossi, 2013 - ''Plasma Membrane Calcium ATPase Activity Is Regulated by Actin Oligomers through Direct Interaction'' - The Journal of Biological Chemistry, p.288, 23380-23393, http://www.jbc.org/content/288/32/23380.full.</ref>.

Another example of regulation. The plasma membrane calcium pump carboxy-terminal tail contains the calmodulin binding domain (regulatory domain) which acts as an auto-inhibitory domain. The binding of the calmodulin frees the pump from autoinhibition.

== Dysfunctions and Diseases ==

Sandbox Reserved 970: Difference between revisions

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 == Regulations ==
-There are different kind of calcium ATPase regulations. For example, the phospholamban (PLN or PLB) is a  membrane protein that regulates the calcium pump in cardiac muscle and skeletal muscle cells. This small phosphoprotein is a pentamer. The phospholamban can be phosphorylated at three distinct sites by various protein kinases (PKA, PKC, CamK...). The phosphorylation state is mediatedthrough beta-adrenergic stimulation. In unphosphorylate state, the phospholamban inhibits the activity of calcium pump in cardiac and skeletal muscle cells by decreasing the apparent affinity of the ATPase for calcium. The phosphorylation of the protein results in the dissociation of the protein from the ATPase. The phosphoprotein binds just downstream of the active ATPase site (asp351).
+There are different kind of calcium ATPase regulations. For example, the phospholamban (PLN or PLB) is a  membrane protein that regulates the calcium pump in cardiac muscle and skeletal muscle cells. This small phosphoprotein is a pentamer. The phospholamban can be phosphorylated at three distinct sites by various protein kinases (PKA, PKC, CamK...). The phosphorylation state is mediated through beta-adrenergic stimulation. In unphosphorylate state, the phospholamban inhibits the activity of calcium pump in cardiac and skeletal muscle cells by decreasing the apparent affinity of the ATPase for calcium. The phosphorylation of the protein results in the dissociation of the protein from the ATPase. The phosphoprotein binds just downstream of the active ATPase site (asp351).
-The activity of the calcium pump is also regulated by by calmodulin, acidic phospholipids and phosphorylation by kinases A and C. Most of the activation mechanisms implicate the C-terminal region of the pump containing the high affinity calmodulin binding domain, which is involved in the autoinhibition of the pump<ref>Marianela G.Dalghi, Marisa M.Fernández, Mariela Ferreira-Gomes, Irene C.Mangialavori, Emilio L.Malchiodi,  Emanuel E.Strehler and Juan Pablo F.C.Rossi, 2013 - ''Plasma Membrane Calcium ATPase Activity Is Regulated by Actin Oligomers through Direct Interaction'' -  The Journal of Biological Chemistry, p.288, 23380-23393, http://www.jbc.org/content/288/32/23380.full.</ref>.
+Most of the activation mechanisms implicate the C-terminal region of the pump containing the high affinity calmodulin binding domain, which is involved in the autoinhibition of the pump<ref>Marianela G.Dalghi, Marisa M.Fernández, Mariela Ferreira-Gomes, Irene C.Mangialavori, Emilio L.Malchiodi,  Emanuel E.Strehler and Juan Pablo F.C.Rossi, 2013 - ''Plasma Membrane Calcium ATPase Activity Is Regulated by Actin Oligomers through Direct Interaction'' -  The Journal of Biological Chemistry, p.288, 23380-23393, http://www.jbc.org/content/288/32/23380.full.</ref>.
+Another example of regulation. The plasma membrane calcium pump carboxy-terminal tail contains the calmodulin binding domain (regulatory domain) which acts as an auto-inhibitory domain. The binding of the calmodulin frees the pump from autoinhibition.
 == Dysfunctions and Diseases ==