Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.74748388
Activation of a calmodulin ( CaM ) dependent protein kinase associated with rabbit skeletal muscle sarcoplasmic reticulum ( SR ) results in the phosphorylation of polypeptides of 450 , 360 , 165 , 105 , 89 , 60 , 34 and 20 kDa . 0.74748388^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.58368871
Skeletal muscle triadin is a sarcoplasmic reticulum ( SR ) membrane protein that had been shown to interact structurally and functionally at the cytoplasmic domain ( amino acid residues 1 47 ) with the ryanodine receptor ( RyR 1 ) , and to undergo phosphorylation by endogenous calmodulin protein kinase ( CaM K 2 ) in isolated terminal cisternae from rabbit fast twitch muscle . 0.58368871^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The cytoplasmic tails of the secretin receptor and the growth hormone releasing hormone receptor either interact poorly or not at all with calmodulin , respectively . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Relaxation depends on reduction of cytosolic ( Ca ) and occurs via 1 ) Ca pumping into the longitudinal SR modulated by phospholamban ; 2 ) the recently cloned high capacity electrogenic SL Na Ca exchanger ; and 3 ) the SL Ca pump under complex regulation including calmodulin control . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The PM Ca2+ pumps are stimulated by calmodulin , the SR Ca2+ pumps encoded by SERCA 1 and SERCA 2 are stimulated by phospholamban while the product of SERCA 3 may be regulated directly by cAMP dependent protein kinase . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Ca2+ release from skeletal sarcoplasmic reticulum ( SR ) could be regulated by at least three mechanisms : 1 ) Ca2+ , 2 ) calmodulin , and 3 ) Ca2+ / calmodulin dependent phosphorylation . ^^^ The time and concentration dependent inhibition of Ca2+ release from skeletal SR by calmodulin was also studied using passively Ca2+ loaded SR vesicles . ^^^ The hypothesis that Ca2+ / calmodulin dependent phosphorylation of a 60 kDa protein regulates Ca2+ release from skeletal SR was tested by stopped flow fluorometry using passively Ca2+ loaded SR vesicles . ^^^ Approximately 80 % of the initial rates of Ca ( 2+ ) induced Ca2+ release was inhibited by the phosphorylation within 2 min of incubation of the SR with Mg ATP and calmodulin . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Another means of increasing SR Ca2+ cycling was to partially remove the calmodulin dependent control of SR Ca2+ release using the calmodulin inhibitor W 7 . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The role of calmodulin ( CaM ) in modulating calcium ( Ca ) uptake by sarcoplasmic reticulum ( SR ) of vascular smooth muscle was studied in saponin skinned strips of rat caudal artery . ^^^ The results indicate that neither exogenous CaM nor an endogenous CaM pool directly modulates inward Ca transport by the SR of saponin skinned caudal artery . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Cardiac SR Ca 2 ( + ) ATPase . 45Ca uptake and cAMP as well as calmodulin ( CaM ) dependent protein phosphorylation were measured . ^^^ Both Ca 2 ( + ) ATPase and 45Ca uptake by cardiac SR were significantly lower in rats treated with CD ( 25 , 50 or 75 mg / kg ) when compared to control rats . cAMP as well as CaM significantly elevated the 32P binding to SR proteins in vitro to about 70 80 % . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Phosphorylation of SR by the exogenously added catalytic subunit of the cAMP dependent protein kinase or by the addition of calmodulin stimulated the ATP dependent Ca2+ uptake activities both in the control and endotoxin injected dogs . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
However , while calmodulin reversed the inhibition of the SR ATPase by C28W , it failed to reverse that induced by nonphosphorylated phospholamban . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The specificity of these findings was demonstrated by much lower levels of calmodulin dependent phosphorylation in light SR as compared to JTC , and by much lower cyclic AMP dependent kinase activity in both JTC and light SR . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Although ATP dependent sarcoplasmic reticular ( SR ) Ca2+ transport has been reported to decrease in old hearts , virtually nothing appears to be known about the Ca2+ pump activity of SR in aging myocardium in the presence of calmodulin , one of its endogenous activators . ^^^ These results suggest that the activity of the Ca2+ pump in SR of aging hearts is depressed even in the presence of calmodulin . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Treatment of intact SR with a specific calmodulin antagonist , compound 48 / 80 or W 7 , lead to the enhancement of the free oxygen radical mediated reduction of steady state calcium accumulation with little effect on passive calcium permeability and Ca , Mg adenosine triphosphatase activity . ^^^ The effects of free oxygen radicals and the calmodulin antagonists on steady state calcium accumulation , but not on passive calcium permeability , were only observed in the presence of the endogenous calmodulin of SR vesicles . ^^^ Hence , we propose that calmodulin dependent component of calcium fluxes in cardiac SR vesicles is modified directly by free oxygen radicals , and that free oxygen radicals can reduce steady state calcium accumulation due to increased calcium release through a calcium efflux pathway which is inhibited by calmodulin , but not due to reduced catalytic activity of the pump . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The effects of calmodulin on single cardiac and skeletal muscle SR Ca2+ release channels were studied using the planar lipid bilayer vesicle fusion technique . ^^^ Our results suggest that calmodulin can modulate excitation contraction coupling by directly interacting with the SR Ca2+ release channel of cardiac and skeletal muscle . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
To define the role of calmodulin in Ca2+ fluxes behavior of canine masseter muscle sarcoplasmic reticulum ( SR ) vesicles , the effect of condensation product of N methyl p methoxy phenethylamine with formaldehyde ( compound 48 / 80 ) , a selective and powerful inhibitor of calmodulin regulated function , on Ca ( 2+ ) ATPase activity , oxalate supported Ca2+ uptake velocity , and on interaction with Ca2+ permeability and Ca2+ loading at steady state were evaluated . ^^^ The results of this study suggest that calmodulin dependent process plays a functional role in the coupling of ATP hydrolysis and Ca2+ accumulation , perhaps through regulation of Ca2+ release channels in masseter muscle SR membrane . ^^^ Calmodulin dependent component of Ca2+ fluxes in the SR vesicles may be directly modified by compound 48 / 80 , thereby diminishing Ca2+ accumulation without affecting the Ca2+ uptake mechanism . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The potentiation was progressive over several beats under conditions that decreased the rate of Ca2+ accumulation into the SR ( deletion of calmodulin from the solutions ; a decrease of the temperature from 22 to 12 degrees C ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Calcium fluctuations propagate by virtue of focal calcium release from the SR , diffusion through the cytosol ( which is modulated by binding to troponin and calmodulin and sequestration by the SR ) , and subsequently induce calcium release from adjacent release sites of the SR . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Phospholamban ( PLB ) from cardiac sarcoplasmic reticulum ( SR ) was phosphorylated under various conditions by the adenosine cyclic 3 ' , 5 ' phosphate ( cAMP ) dependent and / or the calmodulin dependent protein kinase . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
This is unaccompanied by differences in the stimulating effect of calmodulin on Ca2+ transport in sarcoplasmic reticulum ( SR ) of ischemic heart . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
To gain further insight into the effect of caffeine on Ca2+ flux behavior of canine masseter muscle SR vesicles , the present study focuses on the interaction of steady state Ca2+ accumulation and passive Ca2+ permeability in the presence or absence of endogenous calmodulin ( CaM ) , which is known to regulate Ca2+ release channel . ^^^ Caffeine ( 1 ) produced ruthenium red or endogenous CaM inhibitable reduction of oxalate supported Ca2+ uptake velocity with no effect on Ca2+ , Mg ( 2+ ) ATPase activity ; ( 2 ) reduced steady state Ca2+ uptake ; and ( 3 ) had no effect on the permeability of the SR vesicles to Ca2+ , determined by measuring net efflux of Ca2+ after stopping pump mediated fluxes , suggesting that passive Ca2+ permeability is unimportant pathway for changing steady state Ca2+ accumulation . ^^^ The inhibitory effect of caffeine on steady state Ca2+ uptake was moderately abolished by the removal of endogenous CaM from SR vesicles . ^^^ In summary , the data reveal that caffeine ( 1 ) inhibits oxalate entry pathway via inhibition of CaM , and ( 2 ) directly modifies CaM dependent component of Ca2+ fluxes in the SR and reduces steady state Ca2+ accumulation due to increased Ca2+ release through a Ca2+ efflux pathway which is inhibited by CaM but not due to reduced catalytic activity of the pump ; and that the masseter muscle SR vesicles include IP 3 sensitive Ca2+ release channel . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Whenever Ca influx is activated , this Ca does not directly activate the contractile proteins , but rather triggers the release of Ca from the SR to activate calmodulin . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The observed effect of oxygen radicals and radical scavengers was not seen in the calmodulin depleted SR vesicles . ^^^ O2 , is involved in a mechanism that may cause SR dysfunction , and that the effect of oxygen radicals is calmodulin dependent . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The mechanism by which calmodulin stimulates Ca2+ transport in cardiac microsomal preparations enriched in sarcoplasmic reticulum ( SR ) was investigated . ^^^ Autoradiographic analysis of SR membranes labeled with [ 32P ] ATP revealed two protein bands ( 24 , 500 and 40 , 000 daltons ) phosphorylated in the presence of added calcium and calmodulin that were not observed in the absence of either of these additions to the reaction media . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Junctional sarcoplasmic reticulum ( SR ) vesicles isolated from back muscles of normal and malignant hyperthermia susceptible ( MHS ) pigs were phosphorylated by addition of MgATP in the presence of 5 mM Ca2+ and 1 microM calmodulin ( CaM ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The calmodulin antagonist drugs inhibited the Ca2+ dependent ATPase activity and the ATP dependent Ca2+ uptake , and accelerated the efflux of Ca2+ from isolated SR preparations from both control and MHS skeletal muscle . ^^^ These effects of calmodulin antagonist drugs on SR Ca2+ transport functions were consistent with their in vitro pharmacological effects on control and MHS muscle . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Commun . 137 : 507 512 , 1986 ) , and reduced sarcoplasmic reticulum ( SR ) Ca2+ ATPase activity in response to calmodulin exposure in vitro ( Clin . ^^^ Similarly , Ca2+ ATPase activity measured in SR membranes from chickens as early as 13 days post hatch was also found to be resistant to stimulation in vitro by exogenous calmodulin , whereas the enzyme from normal muscle was calmodulin stimulable . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
A skeletal muscle membrane fraction enriched in sarcoplasmic reticulum ( SR ) contained Ca2+ ATPase activity which was stimulated in vitro in normal chickens ( line 412 ) by 6 nM purified bovine calmodulin ( 33 % increase over control , P less than 0 . 001 ) . ^^^ In contrast , striated muscle from chickens ( line 413 ) affected with an inherited form of muscular dystrophy , but otherwise genetically similar to line 412 , contained SR enriched Ca2+ ATPase activity which was resistant to stimulation in vitro by calmodulin . ^^^ Purified SR vesicles , obtained by calcium phosphate loading and sucrose density gradient centrifugation , showed the same resistance of dystrophic Ca2+ ATPase to exogenous calmodulin as the SR enriched muscle membrane fraction . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We postulated that the contraction by virtue of focal calcium release from the sarcoplasmic reticulum ( SR ) and was stimulated this process together with the processes of diffusion into the cytosol , binding to calmodulin and troponin , sequestration by the SR , and subsequent induction of Ca2+ release from the adjacent SR . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The high Mr proteins bound calmodulin ; they were the principal proteins labeled in the cardiac and skeletal muscle SR subfractions by azido 125I calmodulin . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Calmodulin , cAMP dependent protein kinase and K+ stimulated Ca2+ uptake to similar degrees in SR from both control diabetic rats . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Calmidazolium , a lipophilic cation and putative calmodulin specific antagonist , inhibited potently the calcium ATPase of sarcoplasmic reticulum ( SR ) vesicles isolated from skeletal muscle . ^^^ Our results show that calmidazolium is a high affinity , noncompetitive inhibitor of skeletal SR CaATPase activity , and they suggest that this inhibition is based on binding to the membrane phospholipids rather than specific antagonism of enzyme activation by calmodulin . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Washing with 1 mM EGTA , though , did not release any calmodulin from SR . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Two endogenous protein kinase activities , cAMP dependent and calmodulin Ca2+ dependent , are associated with isolated cardiac sarcoplasmic reticulum ( SR ) vesicles . ^^^ Phosphorylation of SR vesicles by both kinases is additive and the extent of saturation of the cAMP specific sites has no effect on the degree of stimulation by calmodulin or its Ca2+ dependence . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
A 58 kDa protein in sarcoplasmic reticulum ( SR ) and sarcolemma ( SL ) of rabbit skeletal muscle was endogenously phosphorylated in a calmodulin dependent manner . ^^^ The 58 kDa protein in SR and SL was considered to be identical to the subunit of cytosol calmodulin kinase on the basis of immunoreactivity , calmodulin binding , and autophosphorylation studies and on the patterns of protease treated phosphopeptides . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Affinity labeling of calmodulin binding proteins in skeletal muscle sarcoplasmic reticulum . 125I Calmodulin ( 125I CaM ) binding to sarcoplasmic reticulum ( SR ) membranes isolated from skeletal muscle cells was investigated , and the CaM receptors associated with the membrane were identified by using the photoaffinity cross linker methyl 4 azidobenzimidate or the chemical cross linker dithiobis N hydroxysuccinimidyl propionate . ^^^ The major labeled protein ( 60 kDa ) probably represents the CaM dependent component involved in Ca2+ release from SR , whereas the others represent a previously unrecognized class of CaM receptors in skeletal SR . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The effect of calmodulin and calmodulin inhibitors on the `` Ca2+ release channel ' ' of `` heavy ' ' skeletal muscle sarcoplasmic reticulum ( SR ) vesicles was investigated . ^^^ SR vesicles were passively loaded with 45Ca2+ in the presence of calmodulin and its inhibitors , followed by measurement of 45Ca2+ release rates by means of a rapid quench Millipore filtration method . ^^^ Heavy SR vesicle fractions contained 0 . 1 02 micrograms of endogenous calmodulin / mg of vesicle protein . ^^^ Studies with actively loaded vesicles also suggested that heavy SR vesicles contain a Ca2+ permeation system that is inhibited by calmodulin . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In Western blots of SR proteins , the 54 / 52 kDa polypeptides were recognized by an antibody specific for the delta CaM kinase isoforms , but not by an anti alpha CaM kinase . ^^^ The two polypeptides were selectively immunoprecipitated from solubilized SR vesicles with the anti delta CaM kinase . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The calmodulin binding properties of the rabbit skeletal muscle Ca2+ release channel ( ryanodine receptor ) and the channel ' s regulation by calmodulin were determined at < or = 0 . 1 microM and micromolar to millimolar Ca2+ concentrations . [ 125I ] Calmodulin and [ 3H ] ryanodine binding to sarcoplasmic reticulum ( SR ) vesicles and purified Ca2+ release channel preparations indicated that the large ( 2200 kDa ) Ca2+ release channel complex binds with high affinity ( KD = 5 25 nM ) 16 calmodulins at < or = 0 . 1 microM Ca2+ and 4 calmodulins at 100 microM Ca2+ . ^^^ SR vesicle 45Ca2+ flux , single channel , and [ 3H ] ryanodine bind measurements showed that , at < or = 0 . 2 microM Ca2+ , calmodulin activated the Ca2+ release channel severalfold . ^^^ These results suggest a role for calmodulin in modulating SR Ca2+ release in skeletal muscle at both resting and elevated Ca2+ concentrations . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
On the other hand , prephosphorylation of the SR by the endogenous CaM kinase and subsequent transfer of the membranes to the Ca2+ transport assay medium results in stimulation of Ca2+ uptake activity ( 202 % of control ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We review data showing that the sarcoplasmic reticulum ( SR ) can buffer ( attenuate ) increases in Cam by : 1 ) sequestering a fraction of Ca entering the cell via sarcolemmal influx pathways , and 2 ) slowly releasing Ca from the SR toward the sarcolemma for extrusion from the cell , thereby decreasing subsequent agonist induced Cam transients and contraction so called `` SR Ca unloading . ' ' Endurance exercise trained ( EX ) , not sedentary ( SED ) , Yucatan miniature pigs show SR Ca unloading via a ryanodine sensitive SR Ca release pathway . ^^^ Mildly increased resting Cam in EX cells may reflect a constant leak of Ca from the SR . ^^^ Collectively , these data indicate altered Cam regulation by the SR in coronary artery of EX animals . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The fast Ca2+ buffering measured in this manner agrees reasonably with the characteristics of known rapid Ca buffers ( e . g . , troponin C , calmodulin , and SR Ca ATPase ) , but is only about half of the total Ca2+ buffering measured at equilibrium . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Three proteins having Mr of 20 000 , 35 000 , and 57 000 were phosphorylated by a calmodulin dependent system in fast skeletal muscle sarcoplasmic reticulum ( SR ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
TFP interacts strongly , in a Ca2+ dependent way , with two SR proteins , calmodulin and the 53 , 000 dalton glycoprotein . ^^^ The inhibition of SR activity by TFP was correlated with the interaction of the drug with the glycoprotein , rather than with calmodulin . ^^^ Calmodulin dependent phosphorylation of three proteins ( Mr = 57 , 000 , 35 , 000 , and 20 , 000 ) of the SR membrane of fast skeletal muscle was also demonstrated . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We have demonstrated recently that in cardiac sarcoplasmic reticulum ( SR ) , a membrane associated Ca2+ / calmodulin dependent protein kinase ( CaM kinase ) phosphorylates and activates the Ca ( 2+ ) pumping ATPase ( Ca ( 2+ ) ATPase ) in addition to phosphorylating the previously characterized substrates , phospholamban , and Ca2+ release channel ( ryanodine receptor ) ( Xu , A . , Hawkins , C . , and Narayanan , N . ( 1993 ) J . ^^^ Incubation of SR vesicles isolated from rabbit slow twitch ( soleus ) and fast twitch ( adductor magnus ) skeletal muscles in the presence of Ca2+ and calmodulin resulted in phosphorylation of the Ca ( 2+ ) ATPase in slow twitch muscle SR but not in fast twitch muscle SR . ^^^ In addition , Ca2+ / calmodulin dependent prephosphorylation of slow twitch muscle SR resulted in a greater than 2 fold increase in its Ca2+ transport activity . ^^^ In both cardiac and slow twitch muscle SR , phosphorylation of the Ca ( 2+ ) ATPase by the endogenous CaM kinase occurred rapidly ( maximum within 2 min at 37 degrees C ) , had similar pH optimum ( 8 . 5 9 . 0 ) , temperature optimum ( 30 degrees C ) , and calmodulin concentration dependence ( k0 . 5 50 60 nM ) . cAMP dependent protein kinase did not phosphorylate the Ca ( 2+ ) ATPase appreciably in either cardiac or slow twitch muscle SR . ^^^ The present study shows that a CaM kinase regulatory system capable of modulating SR Ca2+ pump activity through direct phosphorylation of the Ca ( 2+ ) ATPase is functional in slow twitch but not fast twitch skeletal muscle . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The interaction of the Ca2+ binding protein calmodulin ( CaM ) with the ryanodine receptor of the sarcoplasmic reticulum ( SR ) of pig skeletal muscle was investigated by [ 3H ] ryanodine binding , planar bilayer recordings , and rapid filtration of 45Ca ( 2+ ) loaded SR . ^^^ Rapid filtration of 45Ca2+ passively loaded into SR vesicles showed that CaM blocked Ca2+ release within milliseconds of exposure of SR to a Ca2+ release medium containing 10 microM CaM . ^^^ These results are compatible with a direct mechanism of Ca2+ release channel blockade by CaM and suggest that CaM could play a significant role in the inactivation of SR Ca2+ release during excitation contraction coupling . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Thus , in quiescent myocytes , cytoplasmic and intramitochondrial buffers , rather than transsarcolemmal Ca2+ influx or SR Ca2+ release , are the likely Ca2+ sources for the increase in Cai and Cam , respectively ; additionally , Ca2+ efflux from the mitochondria may contribute to the raise in Cai . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In human SR , a notable amount of PDE 1 hydrolyzing both cAMP and cGMP was characterized ; however , its stimulation by calmodulin was reduced . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Studies were initiated to define the equilibria of calmodulin binding to the skeletal muscle sarcoplasmic reticulum ( SR ) Ca ( 2+ ) release channel protein in native SR vesicles . ^^^ Calmodulin affinity labeling experiments indicated that the major calmodulin receptor in heavy SR preparations was a protein of M ( r ) > 450 , 000 , corresponding to the Ca ( 2+ ) release channel protein . [ 3H ] Ryanodine binding assays indicated 10 . 6 + / 0 . 9 pmol of high affinity ryanodine binding per milligram of SR protein . ^^^ The affinity and binding capacity of the channel protein in SR vesicles for the derivatized calmodulin ( Rh CaM ) were determined by fluorescence anisotropy in the presence of ( 1 ) 1 mM EGTA , ( 2 ) 0 . 1 mM CaCl 2 , and ( 3 ) 0 . 1 mM CaCl 2 plus 1 mM MgCl 2 . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Limited proteolysis and affinity labeling techniques have been used to localize the calmodulin binding domain of phospholamban , the major substrate for both cAMP and calmodulin dependent protein kinases in cardiac sarcoplasmic reticulum ( SR ) . ^^^ SR vesicles , treated with increasing concentrations of trypsin ( likely hydrolyzing at Arg 25 in the cytoplasmic region of phospholamban ) , exhibited a subsequent loss of both cAMP and calmodulin dependent phosphorylation , as well as calmodulin affinity labeling of phospholamban . ^^^ When SR vesicles were treated with increasing concentrations of Endoproteinase Lys C ( which hydrolyzes phospholamban at Lys 3 ) both the calmodulin affinity labeling and the calmodulin dependent , but not the cAMP dependent , phosphorylation of phospholamban were inhibited . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
It is well known that phosphorylation of the membrane protein phospholamban by cAMP dependent or Ca2+ / calmodulin dependent protein kinase results in the activation of the Ca ( 2+ ) pumping ATPase of cardiac sarcoplasmic reticulum ( SR ) ; such enzyme activation is thought to be due to the disruption of an inhibitory interaction of non phosphorylated phospholamban with the ATPase . ^^^ We describe here a novel mechanism for the regulation of the ATPase through direct phosphorylation of this enzyme by a Ca2+ / calmodulin dependent protein kinase ( CaM kinase ) associated with the SR membrane . ^^^ It is shown that incubation of cardiac SR in the presence of Ca2+ and calmodulin results in the phosphorylation of the ATPase in addition to the previously recognized substrates of CaM kinase , viz . phospholamban and Ca2+ channel . ^^^ Furthermore , ATPase purified from cardiac SR is phosphorylated by exogenous CaM kinase and the phosphorylated enzyme displays 2 fold increase in catalytic activity without any appreciable change in its Ca2+ sensitivity . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In the presence of calmodulin ( CaM , 0 . 1 mumol / L per microgram SR vesicles ) , Ca2+ ( 3 mumol / L to 1 mmol / L ) added to the cis solution reduced the channel openings in a concentration dependent fashion , whereas Ca2+ ( 1 nmol / L to 1 mmol / L ) alone or CaM ( 0 . 1 to 1 mumol / L per microgram SR vesicles ) with 1 nmol / L Ca2+ did not affect the channel activity . ^^^ Thus , the cardiac SR 116 picosiemen Cl channel is regulated not only by protein kinase A dependent phosphorylation but also by the cytosolic Ca ( 2+ ) CaM complex . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Porcine skeletal and cardiac muscle sarcoplasmic reticulum ( SR ) vesicle fractions enriched in the ryanodine receptor were phosphorylated in the presence of [ gamma 32P ] MgATP and either exogenous cAMP dependent protein kinase ( cAMP PK ) , or Ca2+ plus calmodulin . ^^^ Phosphorylation of the cardiac muscle ryanodine receptor in the presence of either cAMP PK or calmodulin ( 6 . 4 and 10 . 6 pmol Pi / mg SR respectively ) was approximately equal to or twice the [ 3H ] ryanodine binding activity of this preparation ( 5 . 2 pmol / mg ) . ^^^ 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 ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We analysed the effect of calmodulin on Ca ( 2+ ) induced Ca2+ release ( CICR ) in the sarcoplasmic reticulum ( SR ) using chemically skinned fibres of rabbit psoas muscle . ^^^ Co application of ryanodine and calmodulin at 0 . 3 microM Ca2+ , but not ryanodine alone , induced a decline in the Ca2+ uptake capacity of the SR , an effect expected from the open lock of active CICR channels by ryanodine . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The regulation of the cardiac Ca2+ release channel ryanodine receptor ( RyR ) by exogenous acid phosphatase ( AcPh ) and purified Ca ( 2+ ) calmodulin dependent protein kinase 2 ( CaMKII ) was studied in swine and rabbit sarcoplasmic reticulum ( SR ) vesicles using [ 3H ] ryanodine binding and planar bilayer reconstitution experiments . 2 . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We conclude from these findings , and the additional negative evidence for changes in membrane density of specific components of junctional SR , including 60 kDa Ca ( 2+ ) calmodulin protein kinase , that this membrane domain , like the Ca ( 2+ ) pump domain of the SR , are in no way basically altered at early stages of the aging process , as investigated here . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Calmodulin ( CaM ) has a biphasic effect on Ca ( 2+ ) induced Ca2+ release ( CICR ) from the sarcoplasmic reticulum ( SR ) : potentiation and inhibition at low ( pCa > 6 . 0 ) and high ( pCa 5 ) Ca2+ concentrations , respectively . ^^^ Calmodulin ( CaM ) has a biphasic effect on Ca ( 2+ ) induced Ca2+ release ( CICR ) from the sarcoplasmic reticulum ( SR ) : potentiation and inhibition at low ( pCa > 6 . 0 ) and high ( pCa 5 ) Ca2+ concentrations , respectively . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In cardiac muscle , a Ca2+ / calmodulin dependent protein kinase ( CaM kinase ) associated with the sarcoplasmic reticulum ( SR ) is known to phosphorylate the membrane proteins phospholamban , Ca ( 2+ ) ATPase , and Ca ( 2+ ) release channel ( ryanodine receptor ) . ^^^ In this study , we investigated the effects of the SR Ca ( 2+ ) release inhibitor , ruthenium red ( RR ) , and the SR Ca ( 2+ ) release activator , ryanodine ( at submicromolar concentrations ) , on CaM kinase mediated phosphorylation of the Ca ( 2+ ) cycling proteins in rabbit cardiac SR . ^^^ Incubation of SR with RR ( 5 30 microM ) for 3 min at 37 degrees C resulted in marked ( up to 85 % ) inhibition of Ca2+ channel phosphorylation ( 50 % inhibition with 15 + / 2 microM RR ) by the endogenous membrane associated CaM kinase . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The only documented , apparently specific molecular changes associated with this process in the SR of DM muscle , are the defective expression of the slow / cardiac isoform of Ca ( 2+ ) binding protein calsequestrin , together with an increased phosphorylation activity of membrane bound 60 kDa Ca ( 2+ ) calmodulin ( CaM ) dependent protein kinase . ^^^ Animal studies showed that endogenous Ca ( 2+ ) CaM protein kinase exerts a dual activatory role on SERCA2a SR Ca ( 2+ ) ATPase , i . e . either by direct phosphorylation of the Ca ( 2+ ) ATPase protein , or mediated by phosphorylation of PLB . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Because both SERCA2a and SERCA2b contain this calmodulin kinase phosphorylation site , we examined the effect of endogenous calmodulin kinase phosphorylation of the SR Ca2+ pump in the coronary artery . ^^^ SR enriched membranes were isolated from coronary artery smooth muscle and washed in ethylene glycol bis ( beta aminoethyl ether ) N , N , N ' , N ' tetraacetic acid to remove bound calmodulin . ^^^ The stimulation of Ca2+ uptake was inhibited by including the SR Ca2+ pump inhibitors thapsigargin and cyclopiazonic acid in the Ca2+ uptake medium or by including the calmodulin antagonist N ( 6 aminohexyl ) 5 chloro 1 naphthalenesulfonamide or the calmodulin kinase 2 peptide fragment 290 309 in the phosphorylation solution . ^^^ Therefore , the regulation of the SR Ca2+ pump activity in coronary artery smooth muscle may involve a direct phosphorylation of the pump protein by an endogenous calmodulin dependent kinase . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
To determine if an abnormal calmodulin ( CaM ) regulation of the SR Ca ( 2+ ) release channel ryanodine receptor complex ( RYR 1 ) contributes to this hypersensitivity , we investigated the effect of CaM on high affinity [ 3H ] ryanodine binding to isolated SR vesicles from normal and MHS pig skeletal muscle . ^^^ It is suggested that in vivo an enhanced CaM sensitivity of RYR 1 might contribute to the abnormal high release of Ca2+ from the SR of MHS muscle . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
PKA catalyzed and CAM kinase catalyzed phosphorylation residues ( Ser 16 and Thr 17 ) are located in the N terminal cytoplasmic domain , whereas the C terminal 22 residues are extremely hydrophobic and are considered to be embedded in the SR membrane . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Exogenously added cyclic AMP dependent protein kinase ( A PK ) or calmodulin ( CAM ) increased SR calcium uptake activity . ^^^ In the SR isolated from the treated myocytes , the stimulatory effects of A PK and CAM were also seen , although under all assay conditions calcium uptakes were of lower magnitude . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In the adult myocardium the Ca2+ uptake and release functions of the sarcoplasmic reticulum ( SR ) are known to be regulated by a membrane associated Ca2+ calmodulin dependent protein kinase ( CaM kinase ) which phosphorylates the Ca2+ pumping ATPase ( Ca2+ pump ) , Ca2+ release channel ( ryanodine receptor ) and the Ca2+ pump regulatory protein , phospholamban . ^^^ This phosphorylation could be elicited with the addition of only Ca2+ and calmodulin indicating the presence of a SR associated CaM kinase as early as 21 days gestation . ^^^ Activation of SR CaM kinase with Ca2+ and calmodulin , or induction of phospholamban phosphorylation by exogenous PKA , resulted in stimulation of the Ca2+ uptake activity of SR in fetal , newborn and adult heart . ^^^ The present study investigated the ontogenetic expression of SR associated CaM kinase in the rabbit myocardium as well as development related changes in CaM kinase mediated phosphorylation of the SR proteins ( Ca2+ pump , Ca2+ release channel and phospholamban ) involved in transmembrane Ca2+ cycling . ^^^ These results demonstrate early ontogenetic expression of the Ca2+ cycling proteins and CaM kinase in the SR and the concurrent development of phosphorylation dependent regulation of SR Ca2+ cycling . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The aim of the present study was to investigate the effects of cholecystokinin ( CCK ) CCK ( A ) and CCKB receptor antagonists SR 27897 B , devazepide , L 365260 and PD 135158 ( CAM 1028 ) on exploratory behaviour in the elevated zero maze in the rat . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Posphorylation of the Ca ( 2+ ) ATPase is rapid and is reversible by a membrane associated protein phosphatase , Ca ( 2+ ) ATPase purified from cardiac SR underwent phosphorylation by exogenous CaM kinase , and the phosphorylated enzyme displayed twofold greater catalytic activity without alteration in its Ca ( 2+ ) sensitivity . ^^^ These observations suggest that in cardiac and slow twitch skeletal muscle direct phosphorylation of the SR Ca ( 2+ ) ATPase by the membrane bound CaM kinase may serve to stimulate Ca2+ sequestration and therefore , the speed of muscle relaxation . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Retention of peripheral proteins , like CS and histidine rich Ca ( 2+ ) binding protein , although not that endogenous CaM , and of a unique set of CaM binding proteins , unlike that of junctional SR specific integral proteins , is shown to be influenced by the concentration of Ca2+ during incubation of TC vesicles with Chaps . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
No significant differences in [ 3H ] dantrolene binding characteristics to SR membranes from the two muscle types were detected , and the Bmax ratio for [ 3H ] dantrolene / [ 3H ] ryanodine was 1 . 4 ( + / 0 . 1 ) : 1 in both muscle types . [ 3H ] Dantrolene binding is unaffected by the RyR modulators caffeine , ryanodine , Ruthenium Red and calmodulin , and neither dantrolene nor azumolene have any effect on [ 3H ] ryanodine binding . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The results showed that ( 1 ) the activity of Ca ( 2+ ) ATPase of SR and mitochrondria of myocardium decreased after heat exposure , ( 2 ) the calcium content of SR and mitochrondria also showed a tendency of decrease with increase of exposure temperature , ( 3 ) the 45Ca uptake and mean [ Ca2+ ] 1 increased , whereas the calmodulin content decreased . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We confirmed that superoxide anion radical ( O 2 ) generated from hypoxanthine xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles ; hypoxanthine xanthine oxidase also decreases Ca2+ free within the intravesicular space of the SR with no effect on Ca2+ ATPase activity . ^^^ For the first time , we show that O 2 stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O 2 . ^^^ The decreased calmodulin content induced by oxygen derived free radicals , especially O 2 , is a likely mechanism of accumulation of cytosolic Ca2+ ( due to increased Ca2+ release from SR ) after reperfusion of the ischemic heart . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In addition to measuring changes in cyclic adenosine monophosphate ( cAMP ) protein kinase and Ca ( 2+ ) calmodulin induced phosphorylation , alterations in SR phospholipid composition as well as sulfhydryl ( SH ) group content were investigated . ^^^ The SR Ca ( 2+ ) stimulated ATPase activities in the presence of both cAMP dependent protein kinase and Ca ( 2+ ) calmodulin were markedly decreased in the failing hearts when compared to control preparations . ^^^ Furthermore , the 32P incorporation in the presence of cAMP dependent protein kinase or Ca ( 2+ ) calmodulin was also reduced in the experimental heart SR membranes . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Ca2+ / calmodulin dependent protein kinase 2 ( CaM kinase 2 ) is present in a membrane bound form that phosphorylates synapsin 1 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 . ^^^ We demonstrate that alphaKAP , a non kinase protein encoded by a gene within the gene of alpha CaM kinase 2 , can target the CaM kinase 2 holoenzyme to the SR membrane . ^^^ A new variant of beta CaM kinase 2 , termed betaM CaM kinase 2 , is one of the predominant CaM kinase 2 isoforms associated with alphaKAP in skeletal muscle SR . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In attempting to further define the underlying mechanisms , the present study investigated the impact of aging on the contents of major SR Ca2+ cycling proteins and SR protein phosphorylation by endogenous Ca2+ / calmodulin dependent protein kinase ( CaM kinase ) . ^^^ ATP dependent Ca2+ uptake activity of SR and the stimulatory effect of calmodulin on Ca2+ uptake were also reduced significantly with aging . ^^^ The rates of Ca2+ uptake by PLBab treated SR were significantly lower ( 45 55 % ) in the aged compared with adult rat in the absence and presence of calmodulin . ^^^ Ca2+ ATPase but not PLB underwent phosphorylation by CaM kinase in PLBab treated SR with resultant stimulation of Ca2+ uptake . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We confirmed that superoxide anion radical ( O2 . ) generated from hypoxanthine xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles . ^^^ We directly demonstrate that activation of the channel by O2 . stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2 . . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
A 0 . 6 ms hw ACT was sufficient for the N terminal of CaM to transiently bind approximately 60 % of myosin light chain kinase ( MLCK ) , while a 1 . 8 ms hw ACT produced approximately 22 % transient activation of the sarcoplasmic reticulum ( SR ) Ca2+ / ATPase . ^^^ In both cases , the ACT had fallen back to baseline approximately 10 30 ms before maximal binding of CaM to MLCK or SR Ca2+ / ATPase activation occurred and binding and enzyme activation persisted long after the Ca transient had subsided . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Recent studies have demonstrated phosphorylation of the cardiac and slow twitch muscle isoform ( SERCA2a ) of the sarcoplasmic reticulum ( SR ) Ca2+ ATPase ( at Ser 38 ) by a membrane associated Ca2+ / calmodulin dependent protein kinase ( CaM kinase ) . ^^^ In the present study , we achieved selective phosphorylation of the Ca2+ ATPase by endogenous CaM kinase in isolated rabbit cardiac SR vesicles utilizing a PLN monoclonal antibody ( PLN AB ) which inhibits PLN phosphorylation , and the RYR CRC blocking drug , ruthenium red , which inhibits phosphorylation of RYR CRC . ^^^ Analysis of the Ca2+ concentration dependence of ATP energized Ca2+ uptake by SR showed that endogenous CaM kinase mediated phosphorylation of the Ca2+ ATPase , in the absence of PLN and / or RYR CRC phosphorylation , results in a significant increase ( approximately 50 70 % ) in the Vmax of Ca2+ sequestration without any change in the k0 . 5 for Ca2+ activation of the Ca2+ transport rate . ^^^ These findings suggest that , besides PLN phosphorylation , direct phosphorylation of the Ca2+ ATPase by SR associated CaM kinase serves to enhance the speed of cardiac muscle relaxation . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
CONCLUSIONS : Increased CaM kinase activity in hearts from patients with dilated cardiomyopathy could play a role in the abnormal Ca2+ handling of the SR and heart muscle cell . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Large changes in SPR signals were also observed for Sr ( 2+ ) , Ba ( 2+ ) , Cd ( 2+ ) , Pb ( 2+ ) , Y ( 3+ ) and trivalent lanthanide ions , thereby indicating that not only Ca ( 2+ ) but also these metal ions induce the formation of CaM M 13 metal ion ternary complex . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Calmodulin ( CaM ) and Ca ( 2+ ) / CaM dependent protein kinase 2 ( CaM kinase ) are tightly associated with cardiac sarcoplasmic reticulum ( SR ) and are implicated in the regulation of transmembrane Ca ( 2+ ) cycling . ^^^ Calmodulin ( CaM ) and Ca ( 2+ ) / CaM dependent protein kinase 2 ( CaM kinase ) are tightly associated with cardiac sarcoplasmic reticulum ( SR ) and are implicated in the regulation of transmembrane Ca ( 2+ ) cycling . ^^^ In order to assess the importance of membrane associated CaM in modulating the Ca ( 2+ ) pump ( Ca ( 2+ ) ATPase ) function of SR , the present study investigated the effects of a synthetic , high affinity CaM binding peptide ( CaM BP ; amino acid sequence , LKWKKLLKLLKKLLKLG ) on the ATP energized Ca ( 2+ ) uptake , Ca ( 2+ ) stimulated ATP hydrolysis , and CaM kinase mediated protein phosphorylation in rabbit cardiac SR vesicles . ^^^ The results revealed a strong concentration dependent inhibitory action of CaM BP on Ca ( 2+ ) uptake and Ca ( 2+ ) ATPase activities of SR ( 50 % inhibition at approximately 2 3 microM CaM BP ) . ^^^ The inhibition , which followed the association of CaM BP with its SR target ( s ) , was of rapid onset ( manifested within 30 s ) and was accompanied by a decrease in 5 ( max ) of Ca ( 2+ ) uptake , unaltered K ( 0 . 5 ) for Ca ( 2+ ) activation of Ca ( 2+ ) transport , and a 10 fold decrease in the apparent affinity of the Ca ( 2+ ) ATPase for its substrate , ATP . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The Ca2+ / calmodulin dependent protein kinase associated with the sarcoplasmic reticulum membranes ( SR CaM kinase ) plays a specific and important role in the modulation of both Ca2+ uptake and release functions of the sarcoplasmic reticulum itself . ^^^ Differently from what was previously suggested , our analysis shows that the biochemical properties of the purified SR CaM kinase ( Ca2+ sensitivity , K0 . 5 for calmodulin , Km for ATP , IC 50 for the specific inhibitory peptide ( 290 309 ) , autophosphorylation properties ) are not significantly different from those of the soluble multifunctional CaM kinase 2 . ^^^ Moreover , we show that the purified SR CaM kinase retains the ability to autophosphorylate in a Ca2+ / calmodulin dependent manner , becoming a Ca2+ independent enzyme . ^^^ In this work we have localized a 60 kD SR CaM kinase in slow and fast twitch rabbit skeletal muscle fractions ; the kinase was present in both the longitudinal and the junctional sarcoplasmic reticulum . ^^^ In the light of the knowledge of the rabbit SR CaM kinase biochemical properties , we propose and discuss the possibility that , under physiological conditions , the activity of the autophosphorylated kinase persists when the Ca2+ transient is over . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
A comparison of sucrose density purified SR of rat and rabbit slow twitch muscle , with regard to protein compositional and phosphorylation properties , demonstrates that the biodiversity is two fold , i . e . ( a ) in PLB membrane density ; and ( b ) in the ability of membrane bound Ca ( 2+ ) calmodulin ( CaM ) dependent protein kinase 2 to phosphorylate both PLB and SERCA2a ( slow twitch isoform of Ca ( 2+ ) ATPase ) . ^^^ The basal phosphorylation state of PLB at Thr 17 in isolated SR vesicles from rabbit slow twitch muscle , colocalization of CaM K 2 with PLB and SERCA2a at the same membrane domain , and the divergent subcellular distribution of PKA , taken together , seem to argue for a differential heterogeneity in the regulation of Ca ( 2+ ) transport between such muscle and heart muscle . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The hypothesis that calmodulin ( CaM ) may act as a positive modulator of junctional SR Ca2+ release channel / ryanodine receptor ( RyRl ) rests largerly on the demonstrated capacity of CaM to interact structurally and functionally with RyRl at pCa > 8 ( Tripathy et al . , 1995 ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The effects of a number of phenothiazines and other calmodulin antagonists on the Ca ( 2+ ) ATPase activity of sarcoplasmic reticulum ( SR ) and endoplasmic reticulum ( ER ) were investigated . ^^^ Our results showed that calmidazolium and calmodulin binding peptide were the most potent inhibitors of skeletal muscle SR Ca ( 2+ ) ATPase activity ( isoform SERCA 1 ) ( IC ( 50 ) values of 0 . 5 and 7 microM , respectively ) , while W 7 was the least potent inhibitor ( IC ( 50 ) , 125 microM ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
However , the role of CaM activation in the mechanisms that control Ca ( 2+ ) release from the sarcoplasmic reticulum ( SR ) in skeletal muscle and in the heart remains unclear . ^^^ In media that contained 100 nM Ca ( 2+ ) , the rate of ( 45 ) Ca ( 2+ ) release from porcine skeletal muscle SR vesicles was increased approximately threefold in the presence of CaM ( 1 microM ) . ^^^ In contrast , cardiac SR vesicle ( 45 ) Ca ( 2+ ) release was unaffected by CaM , suggesting that CaM activated the skeletal RyR 1 but not the cardiac RyR 2 channel isoform . ^^^ The activation of RyR 1 by CaM was associated with an approximately sixfold increase in the Ca ( 2+ ) sensitivity of [ ( 3 ) H ] ryanodine binding to skeletal muscle SR , whereas the Ca ( 2+ ) sensitivity of cardiac SR [ ( 3 ) H ] ryanodine binding was similar in the absence and presence of CaM . ^^^ Cross linking experiments identified both RyR 1 and RyR 2 as predominant CaM binding proteins in skeletal and cardiac SR , respectively , and [ ( 35 ) S ] CaM binding determinations further indicated comparable CaM binding to the two isoforms in the presence of micromolar Ca ( 2+ ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Modulation of sarcoplasmic reticulum ( SR ) Ca ( 2+ ) transport by endogenous calmodulin dependent protein kinase 2 ( CaM K 2 ) involves covalent changes of regulatory protein phospholamban ( PLB ) , as a common , but not the only mechanism , in limb slow twitch muscles of certain mammalian species , such as the rabbit . ^^^ Accommodating embryological heterogeneity in the paradigm of neural dependent expression of specific isogenes in skeletal muscle fibers , our results provide novel evidence for the differential expression in the SR of 72 kDa beta components of CaM K 2 , together with the expression of a slow twitch sarcoendoplasmic reticulum Ca ( 2+ ) ATPase isoform , both in limb muscle and in the masseter . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Regulatory phosphorylation of phospholamban and of SR Ca ( 2+ ) ATPase SERCA2a isoform by endogenous CaM K 2 in slow twitch skeletal and cardiac sarcoplasmic reticulum ( SR ) is well documented , but much less is known of the exact functional role of CaM K 2 in fast twitch muscle SR . ^^^ Recently , it was shown that RNA splicing of brain specific alpha CaM K 2 , gives rise to a truncated protein ( alpha KAP ) , consisting mainly of the association domain , serving to anchor CaM K 2 to SR membrane in rat skeletal muscle [ Bayer , K . ^^^ In the present study , we searched for the presence of alpha KAP in sucrose density purified SR membrane fractions from representative fast twitch and slow twitch limb muscles , both of the rabbit and the rat , using immunoblot techniques and antibody directed against the association domain of alpha CaM K 2 . ^^^ Putative alpha KAP was immunodetected as a 23 kDa electrophoretic component on SDS PAGE of the isolated SR from fast twitch but not from slow twitch muscle , and was further identified as a specific substrate of endogenous CaM K 2 , in the rabbit . ^^^ That raises the question of whether CaM K 2 mediated phosphorylation of alpha KAP and triadin together might be involved in a molecular signaling pathway important for SR Ca ( 2+ ) release in fast twitch muscle SR . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
We have previously shown that selective activation of RyR / Ca2+ release channel by superoxide anion radical ( O2 . ) is dependent of the presence of calmodulin and identified calmodulin as a functional mediator of O2 . triggered Ca2+ release through the RyR / Ca2+ release channel of cardiac sarcoplasmic reticulum ( SR ) . ^^^ We now demonstrate that although the effect of O2 . on Ca2+ efflux from RyR / Ca2+ release channel at higher concentrations ( > 5 microM ) is due to its ability to produce a loss in function of calmodulin thereby decreasing calmodulin inhibition , O2 . radicals at lower concentrations ( < 5 microM ) may be able to stimulate Ca2+ release only in the presence of calmodulin from the SR via increased cADPR synthesis ; it is also shown that cADPR is a modulator that can activate the Ca2+ release mechanism when it is in a sensitized state by the presence of calmodulin , possibly , at physiological concentration . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In the presence of calmodulin ( CaM ) ( 0 . 1 microM / microg SR vesicles ) , however , Ca ( 2+ ) added to the cis solution at 0 mV inhibited channel openings in a Ca ( 2+ ) concentration dependent manner . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Our results show that alpha KAP is largely localized at the free SR and thus near the Ca ( 2+ ) pump , a protein that can be modulated by CaM kinase 2 phosphorylation . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Anchoring protein alphaKAP targets calmodulin kinase 2 ( CaMKII ) to the sarcoplasmic reticulum ( SR ) , and in the rabbit is a substrate of CaMKII itself in fast twitch , but not in slow twitch muscle . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
To decipher the mechanism ( s ) underlying glucocorticoid action on cardiac contractile function , this study investigated the effects of adrenalectomy and dexamethasone treatment on the contents of sarcoplasmic reticulum ( SR ) Ca ( 2+ ) cycling proteins , their phosphorylation by endogenous Ca ( 2+ ) / calmodulin dependent protein kinase 2 ( CaM kinase 2 ) , and SR Ca ( 2+ ) sequestration in the rat myocardium . ^^^ However , the relative amount of SR associated CaM kinase 2 protein was increased 2 . 5 to 4 fold in dexamethasone treated rats compared with control and adrenalectomized rats . ^^^ The stimulatory effect of CaM kinase 2 activation on Ca ( 2+ ) uptake activity of SR was significantly depressed after adrenalectomy and greatly enhanced after dexamethasone treatment . ^^^ These findings identify the SR as a major target for glucocorticoid actions in the heart and implicate modification of the SR CaM kinase 2 system as a component of the mechanisms by which dexamethasone influences SR Ca ( 2+ ) cycling and myocardial contraction . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Neither effect could be elicited by a more avid CaM binding peptide , suggesting that generalized CaM buffering did not account for the effects of IQmp . 4 . 1 ( Ca ) facilitation was abolished and the fast component of inactivation eliminated by ryanodine , caffeine or thapsigargin , suggesting that the sarcoplasmic reticulum ( SR ) is an important source of Ca2+ for 1 ( Ca ) facilitation and inactivation . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Accordingly , we show that HRC is preferentially phosphorylated by endogenous CaM K 2 , anchored to SR membrane on the cytoplasmic side , and not by lumenally located casein kinase 2 . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Blockade of sarcoplasmic reticulum ( SR ) function by ryanodine ( 10 microM ) and thapsigargin ( 1 microM ) or a selective inhibitor of Ca ( 2+ ) calmodulin kinase 2 , 2 [ N ( 2 hydroxyethyl ) N ( 4 methoxybenzenesulfonyl ) ] amino N ( 4 chlorocinnamyl ) N methyl benzylamine ( 1 microM ) completely abolished the reacceleration of twitch [ Ca ( 2+ ) ] ( 1 ) decline and almost eliminated the contractile recovery . ^^^ We concluded that during prolonged acidosis , Ca ( 2+ ) calmodulin kinase 2 dependent reactivation of SR Ca ( 2+ ) uptake could increase SR Ca ( 2+ ) content and CaT amplitude . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Of these proteins , calmodulin ( CaM ) and Ca CaM dependent kinase 2 ( CaMKII ) are of special interest in the heart because of their role of modulating Ca influx , SR Ca release , and SR Ca uptake during E C coupling . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
In the presence of intact RyR 1 channels in SR vesicles , ( ACR ) CaM fluorescence spectra were distinct from those in the presence of RyR 1 ( 3614 ) ( ) ( 43 ) , although a Ca ( 2+ ) dependent decrease in fluorescence was still observed . ^^^ The K ( Ca ) for ( ACR ) CaM fluorescence in the presence of SR ( 0 . 8 + / 0 . 4 microM ) was greater than in the presence of RyR 1 ( 3614 ) ( ) ( 43 ) but was consistent with functional determinations showing the conversion of ( ACR ) CaM from channel activator ( apoCaM ) to inhibitor ( Ca ( 2+ ) CaM ) at Ca ( 2+ ) concentrations between 0 . 3 and 1 microM . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
To determine the underlying mechanisms , we examined the properties of L type Ca2+ channels , Ca2+ / CaM dependent protein kinase 2 ( CaMKII ) , and phospholamban ( PLB ) in the sarcoplasmic reticulum ( SR ) . ^^^ Moreover , CaM ( 1 4 ) elevated diastolic Ca2+ and caffeine labile Ca2+ content of the SR . ^^^ These results demonstrate that CaM modulates Ca2+ influx , SR Ca2+ release , and Ca2+ recycling during cardiac EC coupling . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Several proteins involved in SR Ca2+ release are affected by calmodulin kinase 2 ( CaMKII ) induced phosphorylation in vitro , but the effect in the intact cell remains uncertain and is the focus of the present study . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Included in the electrochemical model are models of the electrophysiological behavior of the cell membrane , fluid compartments , Ca2+ release and uptake by the sarcoplasmic reticulum ( SR ) , and cytosolic Ca2+ buffering , particularly by calmodulin ( CM ) . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Further , CaMBP removes CaM associated with SR vesicles and increases [ 3H ] ryanodine binding to purified RyR 1 , suggesting that its mechanism of action is two fold : it removes endogenous inhibitors and also interacts directly with complementary regions in RyR 1 . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
From ED 5 to 15 , troponin C was the major Ca ( 2+ ) binding moiety , followed by SR and calmodulin . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
This study investigated the effects of l thyroxine induced hyperthyroidism on Ca ( 2+ ) / calmodulin ( CaM ) dependent protein kinase ( CaM kinase 2 ) mediated sarcoplasmic reticulum ( SR ) protein phosphorylation , SR Ca ( 2+ ) pump ( Ca ( 2+ ) ATPase ) activity , and contraction duration in slow twitch soleus muscle of the rabbit . ^^^ CaM kinase 2 mediated stimulation of Ca ( 2+ ) uptake by soleus muscle SR was approximately 60 % lower in the hyperthyroid compared with euthyroid . ^^^ These results demonstrate that thyroid hormone induced transition in contractile properties of the rabbit soleus is associated with coordinate downregulation of the expression and function of PLN and CaM kinase 2 and selective upregulation of the expression and function of SERCA 1 , but not SERCA 2 , isoform of the SR Ca ( 2+ ) pump . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The skeletal muscle specific Ca ( 2 ) + / calmodulin dependent protein kinase ( CaMKIIbeta ( M ) ) is localized to the sarcoplasmic reticulum ( SR ) by an anchoring protein , alphaKAP , but its function remains to be defined . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
The presence of a CaMKIIbeta isoform that can target the SR presumably via its membrane anchor alphaKAP defines a previously unrecognized Ca2+ / CaM regulatory system in myocardium . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Here we determine the role of CaM Met residues in the productive association of CaM with RyR 2 , as assessed via determinations of [ 3H ] ryanodine and [ 35S ] CaM binding to cardiac muscle sarcoplasmic reticulum ( SR ) vesicles . ^^^ Substitution of the COOH terminal Mets of CaM with Leu decreased the extent of CaM inhibition of cardiac SR ( CSR ) vesicle [ 3H ] ryanodine binding . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Our findings that caffeine relaxes and hyperpolarizes murine gastric fundus smooth muscles and increases phospholamban ( PLB ) phosphorylation by Ca2+ / calmodulin ( CaM ) dependent protein kinase 2 ( CaM kinase 2 ) suggest that PLB phosphorylation by CaM kinase 2 participates in smooth muscle relaxation by increasing sarcoplasmic reticulum ( SR ) Ca2+ uptake and the frequencies of SR Ca2+ release events and STOCs . ^^^ These results demonstrate a novel pathway linking the NO soluble guanylyl cyclase cGMP pathway , SR Ca2+ release , PLB , and CaM kinase 2 to relaxation in gastric fundus smooth muscles . . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Phosphorylation of sarcoplasmic reticulum ( SR ) Ca2+ cycling proteins by a membrane associated Ca2+ / calmodulin dependent protein kinase 2 ( CaM kinase 2 ) is a well documented physiological mechanism for regulation of transmembrane Ca2+ fluxes and the cardiomyocyte contraction relaxation cycle . ^^^ The present study investigated the effects of L thyroxine induced hyperthyroidism on protein expression of SR CaM kinase 2 and its substrates , endogenous CaM kinase 2 mediated SR protein phosphorylation , and SR Ca2+ pump function in the rabbit heart . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
Previous studies in transgenic mice and with isolated ryanodine receptors ( RyR ) have indicated that Ca2+ calmodulin dependent protein kinase 2 ( CaMKII ) can phosphorylate RyR and activate local diastolic sarcoplasmic reticulum ( SR ) Ca2+ release events ( Ca2+ sparks ) and RyR channel opening . ^^^
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA
Interacting proteins: P47872 and P62158	Pubmed	SVM Score :0.0
NA