Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium initiates smooth muscle contraction by binding to calmodulin and activating the enzyme myosin light chain kinase. The activated form of myosin light chain kinase phosphorylates myosin on the 20,000-dalton light chain and contractile activity ensues. Calcium may also enhance smooth muscle contractile activity by binding directly to myosin, the main component of the thick filament. Recent studies raise the possibility that the calcium-calmodulin complex may also modulate smooth muscle contractile activity by removing the inhibition imposed by caldesmon, a protein that is bound to the thin (i.e., actin-containing) filaments of smooth muscle. In vitro studies have demonstrated that the calcium-activated, phospholipid-dependent kinase, protein kinase C, can phosphorylate smooth muscle myosin at a different site than does myosin light chain kinase and down-regulate its actin-activated magnesium adenosine triphosphatase activity. This raises the possibility that protein kinase C phosphorylation of myosin may play a role in modulating vascular contractile activity in vivo.
...
PMID:Effects of calcium on vascular smooth muscle contraction. 302 18

Control of the contraction/relaxation cycle in vascular smooth muscle is regulated by Ca2+ and the cyclic nucleotides, cAMP and cGMP. For the most part, the effectors of these intracellular messengers are the protein kinases. Four major protein kinases (myosin light chain kinase, protein kinase C, cAMP dependent protein kinase, and cGMP dependent protein kinase) have been identified in vascular smooth muscle. Substantial biochemical and physiological evidence exists supporting the involvement of Ca2+/calmodulin-mediated activation of myosin light chain kinase and phosphorylation of the 20,000 dalton P-light chain of myosin in the regulation of vascular contractile activity. However, alternative hypotheses exist which suggest that additional Ca2+ dependent regulatory mechanisms reside at other contractile protein sites. Calcium also activates protein kinase C, which requires phospholipid and diacylglycerol as co-factors instead of calmodulin. Protein kinase C also phosphorylates smooth muscle myosin P-light chain; however, phosphorylation occurs at a different site on the P-light chain and represses ATPase activity which has been stimulated by myosin light chain kinase-catalyzed phosphorylation. The precise physiological role of protein kinase C in modulating vascular smooth muscle contractile activity remains to be elucidated. Relaxation of vascular smooth muscle by some different relaxants is linked to either cAMP or cGMP formation. Correlative evidence also links activation of cAMP dependent protein kinase with relaxation. Two isozymes of cAMP dependent protein kinase exist in arterial smooth muscle; potential specific roles for each isozyme have not been elucidated. Mechanistically, relaxation mediated by both cyclic nucleotide-regulated protein kinases most likely involves primary effects on Ca2+ ion flux regulation rather than direct effects on contractile protein interactions. Activation of cGMP dependent protein kinase may be important in mediating the relaxant effects of endothelium derived relaxant factor or atrial natriuretic factor. Direct pharmacological modulation of smooth muscle vascular protein kinase activity represents an approach towards developing novel vasodilator agents. Various classes of agents, including phenothiazine antipsychotics, antidepressants, naphthalene sulfonamides, and certain lipophilic Ca2+ antagonists, inhibit myosin light chain kinase activity primarily by competition with the enzyme for Ca2+-calmodulin. However, additional inhibition via binding to the myosin P-light chain may also occur with some of these agents.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Regulation of contractile activity in vascular smooth muscle by protein kinases. 302 13

Smooth muscle heavy meromyosin (HMM) is phosphorylated by the Ca2+-activated phospholipid-dependent protein kinase, i.e. protein kinase C, at three sites on each 20,000-dalton light chain. Phosphorylation of three sites also is observed with isolated 20,000-dalton light chain and HMM subfragment 1. The phosphorylation sites are serine 1, serine 2, and threonine 9. Threonine is phosphorylated most rapidly followed by either serine 1 or 2. Phosphorylation of the third site occurs only on prolonged incubation. Phosphorylation is a random process. HMM phosphorylated at two sites per light chain by protein kinase C can be dephosphorylated, as shown using two phosphatase preparations. Increasing levels of phosphorylation of HMM by protein kinase C causes a progressive inhibition of the subsequent rate of phosphorylation of serine 19 by myosin light chain kinase and causes a progressive inhibition of actin-activated ATPase activity of HMM, prephosphorylated by myosin light chain kinase. Inhibition of ATPase activity is due to a decreased affinity of HMM for actin rather than a change in Vmax. Previous results with HMM and protein kinase C (Nishikawa, M., Sellers, J. R., Adelstein, R. S., and Hidaka, H. (1984) J. Biol. Chem. 259, 8808-8814) examined effects induced by phosphorylation of the threonine residues. Our results confirm these and consider also the influence of higher levels of phosphorylation by protein kinase C.
...
PMID:Phosphorylation of the 20,000-dalton light chain of smooth muscle myosin by the calcium-activated, phospholipid-dependent protein kinase. Phosphorylation sites and effects of phosphorylation. 303 66

We examined the effects of four Ca2+ antagonists that possess the ability to bind to calmodulin-felodipine, nitrendipine, prenylamine, and verapamil--as well as the effect of the calmodulin antagonist trifluoperazine on Ca2+ uptake and Ca2+ + Mg2+/ATPase activity in canine cardiac sarcoplasmic reticulum. In the presence of 20-30 microM felodipine and 100-200 microM nitrendipine, Ca2+ uptake increased from 69 nmoles X mg-1 X min-1 to 107 and 108 nmoles X mg-1 X min-1, respectively, with half-maximal stimulation occurring at 7.5 and 28 microM respectively. Ca2+ + Mg2+/ATPase activity was unchanged over the same concentration ranges. In contrast, both Ca2+ uptake and Ca2+ + Mg2+/ATPase activities were inhibited in the presence of 10-100 microM trifluoperazine (IC50 = 25 microM), 10-100 microM prenylamine (IC50 = 35 microM) and 100-200 microM verapamil (inhibition insufficient for IC50 determination). None of the drugs affected membrane permeability to Ca2+ as determined by passive 45Ca2+ efflux in the presence of ethyleneglycol bis(beta-amenoethyl ether)N,N,N1-tetraacetic acid (EGTA). Drug inhibition of calmodulin-dependent turkey gizzard myosin light chain kinase activation in a purified protein system was used as a direct measure of calmodulin antagonism, and felodipine, nitrendipine, trifluoperazine, prenylamine, and verapamil blocked this activation at IC50 values of 9.8, 55, 6.4, 31, and 93 microM respectively. None of the drugs studied, however, had any effect upon endogenous phospholamban phosphorylation in our cardiac sarcoplasmic reticulum preparations. These observations indicate that dihydropyridine Ca2+ antagonists stimulate cardiac sarcoplasmic reticulum Ca2+ uptake in vitro either by increasing the efficiency of the transport process or by inhibiting Ca2+-dependent Ca2+ release, and suggest that these effects do not result from interference with calmodulin-mediated processes.
...
PMID:Stimulation of canine cardiac sarcoplasmic reticulum Ca2+ uptake by dihydropyridine Ca2+ antagonists. 315 15

Like other vertebrate nonmuscle myosins, thymus myosin contains two phosphorylatable light chains. Phosphorylation of these light chains regulates the actin-activated ATPase of this myosin. The time courses for the phosphorylation of both monomeric and filamentous thymus myosin by gizzard myosin light chain kinase fitted single exponentials to greater than 85% phosphorylation. This indicates that the two heads of thymus myosin are phosphorylated at the same rate and suggests that these phosphorylations are random processes. The actin-activated ATPases of thymus myosins with different levels of light chain phosphorylation were also determined. A linear relationship was obtained between the extent of light chain phosphorylation and stimulation of the actin-activated ATPase. Since thymus myosin appears to be phosphorylated randomly, this linear relationship indicates that phosphorylation of one head of thymus myosin stimulates the actin-activated ATPase of that head independently of the phosphorylation of the second head. The apparent random phosphorylation of thymus myosin light chains contrasts with the reported ordered phosphorylation of the light chains of filamentous smooth (gizzard) muscle myosin. Also, while the actin-activated ATPases of the two heads of thymus myosin are regulated independently, both heads of gizzard myosin must be phosphorylated before the ATPase of either head is activated by actin.
...
PMID:Random phosphorylation of the two heads of thymus myosin and the independent stimulation of their actin-activated ATPases. 315 23

Previous work from our laboratory indicated that pancreatic islets contain myosin light chain kinase, a calcium- and calmodulin-activated enzyme. This enzyme catalyzes phosphorylation of myosin which, in tissues containing smooth muscle, is believed to permit the ATPase of myosin to be activated by actin. The current report shows that incubating islet cytosol with ATP under conditions that should permit phosphorylation of myosin markedly enhances islet myosin ATPase activity in the presence of actin. It has been suggested that contractile proteins power insulin granule movements in the beta cell. Phosphorylation of myosin may be one of the means of coupling stimuli to insulin secretion.
...
PMID:Activation of pancreatic islet myosin ATPase by ATP and actin. 316 Mar 44

The contraction induced by a Ca2+-independent myosin light chain kinase (MLCK-) was characterized in terms of isometric force (Fo), immediate elastic recoil (SE), unloaded shortening velocity (Vus), shortening under a constant load and ATPase activity of chemically skinned smooth muscle preparations. These parameters were compared to those measured in a Ca2+ -induced contraction to assess the nature of cross bridge interaction in the MLCK-induced contraction. Fo developed in chicken gizzard fibers as well as SE were similar in contractions elicited by either agent. Vus in the contraction induced by MLCK-(0.36 mg/ml) was similar though averaged 39.3 +/- 8.9% less than Vus induced by Ca2+ (1.6 X 10(-6) M) in the control fibers. Addition of Ca2+ (1.6 X 10(-6) M) to a contraction induced by MLCK-resulted in small increases in both Fo and Vus. Shortening under a constant load was similar for both types of contractions. The contraction induced by MLCK-was accompanied by an increased rate of ATP hydrolysis. The MLCK-induced contraction is thus kinetically similar though not identical to a contraction induced by Ca2+. We conclude that with respect to actin-myosin interaction, MLCK-and Ca2+ -induced contractions are similar.
...
PMID:Mechanical and biochemical characterization of the contraction elicited by a calcium-independent myosin light chain kinase in chemically skinned smooth muscle. 316 Jun 2

With large amounts of gizzard Mr 135,000 calmodulin-binding protein (myosin light chain kinase), the phosphate incorporation into myosin light chains was determined to be 2 mol/mol of myosin light chain. The actin-activated ATPase activity was dramatically enhanced when myosin light chains were phosphorylated by more than 1 mol of phosphate incorporated/mol of myosin light chain.
...
PMID:Correlation between multiple phosphorylation of gizzard myosin light chains and actin-activated myosin ATPase activity. 316 77

Controversial views have been reported regarding the role of myosin light chain phosphorylation in the regulation of cardiac contractility (for review see. In the past, adenosine 5'-(-thio)triphosphate) (ATP gamma S) instead of ATP has frequently been used to study mechanical and biochemical consequences of myosin P-light chain (P-LC, LC-2) phosphorylation since thiophosphorylated sites are not significantly attacked by phosphatases. Unlike thiophosphorylation phosphorylation of myosin by myosin light chain kinase did neither decrease maximal (unloaded) shortening velocity of cardiac skinned fibres nor ATPase activity of cardiac myofibrils. We have accordingly investigated the phosphorylation pattern of purified cardiac myosin light chains using radioactive labeled ATP gamma S and ATP. We found that both the 28 kDa myosin light chain (LC-1) and the 18 kDa myosin light chain (LC-2, P-LC) were phosphorylated when ATP gamma S was present. In the presence of ATP, however, only LC-2 was found to be phosphorylated.
...
PMID:Different phosphorylation patterns of cardiac myosin light chains using ATP and ATP gamma S as substrates. 317 47

The 20,000-dalton light chain of turkey gizzard myosin is phosphorylated at two sites. Dual phosphorylation is observed when both intact myosin and isolated light chains are used as substrates. Phosphorylation of the second site is not observed at higher ionic strength (e.g. 0.35 M KCl). The first phosphorylation site (serine 19) is phosphorylated preferentially to the second site. The latter is phosphorylated more slowly than the first site, and its phosphorylation requires relatively high concentrations of myosin light chain kinase. It is suggested that myosin light chain kinase catalyzes the phosphorylation of both sites on the light chain, and several reasons are cited that make it unlikely that a contaminant kinase is involved. The second phosphorylation site is a threonine residue. Based on the results of limited proteolysis of the light chain, it is concluded that the threonine residue is close to serine 19, and possible locations are threonines 9, 10, and 18. At all concentrations of MgCl2, phosphorylation of the second site markedly increases the actin-activated ATPase activity of myosin and accelerates the superprecipitation response of myosin plus actin.
...
PMID:Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase. 383 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---