Discovery of A Ca<sup>2+</sup>‐and calmodulin‐dependent protein phosphatase

Stewart, Alexander A.; Ingebritsen, Thomas S.; Manalan, Allan S.; Klee, Claude B.; Cohen, Philip

doi:10.1016/0014-5793(82)80319-0

Cited by 476 publications

(209 citation statements)

References 21 publications

(4 reference statements)

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“…The discovery of a Ca2 + and calmodulin-dependent protein phosphatase activity in heart sarcolemma is reminiscent of recent observations by Cohen et al [46] who have identified and isolated in skeletal muscle a soluble, Caz+ and calmodulin-dependent phosphatase which acts on inhibitor protein I [47] myosin light chains, and the a-subunit of phosphorylase kinase [46]. The phosphatase described here, however, has a lower effinity for calmodulin than the enzyme described by Cohen et al [46].…”

Section: Discussionsupporting

confidence: 69%

See 1 more Smart Citation

The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma

Caroni¹,

Carafoli²

1983

European Journal of Biochemistry

215

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The Na+/Ca2+ ‐exchange of calf‐heart sarcolemma is activated by a treatment with ATP, Mg2+, and Ca2+, and deactivated by a treatment with phosphorylase phosphatase. The effect of th e latter can be substituted by a treatment with Mg2+, Ca2+, and calmodulin. the activating treatment does not require added calmodulin, but is inhibited by calmodulin antagonists. Evidently, engdogenous calmodulin is required and sufficient. Activation is half‐maximal at about 2μM Ca2+. Added clamodulin, however, decreases the Km (Ca2+) of the activating process to about 0.8 μM. Deactivation is half‐maximal, at optimal calmodulin concentrations, at about 1.5 μM Ca2+. Experiments with adenosine 5′‐[γ‐thio]triphosphate have shown that the activating treatment is mediated by a kinase and the deactivating treatment by a phosphatase. The concerted operation of the two enzymes is made possible by their different Ca2+ affinity. At saturating Ca2+ concentrations, the level of ATP may also influence the balance of the two enzymes.

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Section: Discussionsupporting

confidence: 69%

“…The phosphatase described here, however, has a lower effinity for calmodulin than the enzyme described by Cohen et al [46].…”

Section: Discussioncontrasting

confidence: 61%

The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma

Caroni¹,

Carafoli²

1983

European Journal of Biochemistry

215

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“…-dependent zinc release was documented for endothelin-converting enzyme (35). The gain of CaN Mn 2ϩ dependence during purification was noticed as early as in 1982 (36), and the interaction of Mn 2ϩ with CaN was investigated in detail (13,37), but the present study is to our knowledge the first to connect Mn 2ϩ dependence to a previous oxidative inactivation of the enzyme.…”

Section: Superoxide Inhibition Of Can Activity In Cellular Extractsmentioning

confidence: 87%

Redox Control of Calcineurin by Targeting the Binuclear Fe2+-Zn2+ Center at the Enzyme Active Site

Namgaladze

Hofer

Ullrich

2002

Journal of Biological Chemistry

112

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The interaction of protein serine/threonine phosphatase calcineurin (CaN) with superoxide and hydrogen peroxide was investigated. Superoxide specifically inhibited phosphatase activity of CaN toward RII (DLD-VPIPGRFDRRVSVAAE) phosphopeptide in tissue and cell homogenates as well as the activity of the enzyme purified under reducing conditions. Hydrogen peroxide was an effective inhibitor of CaN at concentrations several orders of magnitude higher than superoxide. Inhibition by superoxide was calcium/calmodulin-dependent. Nitric oxide (NO) antagonized superoxide action on CaN. We provide kinetic and spectroscopic evidence that native, catalytically active CaN has a Fe 2؉ -Zn 2؉ binuclear center in its active site that is oxidized to Fe 3؉ -Zn 2؉ by superoxide and hydrogen peroxide. This oxidation is accompanied by a gain of manganese dependence of enzyme activity. CaN isolated by a conventional purification procedure was found in the oxidized, ferric enzyme form, and it became increasingly dependent on divalent cations. These results point to a complex redox regulation of CaN phosphatase activity by superoxide, which is modified by calcium, NO, and superoxide dismutase.

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“…Therefore, it would be reasonable to hypothesize that the function of CaM in cell cycle control might be mediated either through regulation of CaMdependent kinases or phosphatases. There are several CaMdependent protein kinases (9 -14), and at least one CaM-dependent phosphatase (PP2B or calcineurin) (15). Recent evidence suggests that CaM-dependent protein kinases play a role in cell cycle regulation.…”

mentioning

confidence: 99%

Cloning of a Calmodulin Kinase I Homologue fromSchizosaccharomyces pombe

Rasmussen

2000

Journal of Biological Chemistry

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By using35 S-labeled calmodulin (CaM), we have isolated a full-length cDNA clone expressing the Schizosaccharomyces pombe homologue of calmodulin kinase I (CaMK-I), a gene we have named cmk1. It has been previously been shown in mammals that CaMK-I is a member of a CaM-dependent protein kinase cascade that ultimately regulates transcription factors such as ATF and cAMP-response element-binding protein. The cmk1 cDNA encodes a 335-amino acid protein with significant homology to mammalian CaMK-I, including a conserved sequence for phosphorylation by CaM kinase kinase. We have expressed the cmk1 cDNA in bacteria and yeast, and we have shown that it is a CaM-dependent protein kinase. A truncation mutant of cmk1 (d320) failed to bind CaM, indicating that the CaM-binding domain is at the extreme C terminus of the protein. The mRNA for cmk1 is expressed in a cell cycle-dependent manner, peaking at or near the G 1 /S boundary. Overexpression of wild-type cmk1 in S. pombe caused no apparent effects on growth and division. However, mutation of a predicted regulatory site (Thr-192) to aspartic acid resulted in hyperactivation of CMK1 activity in the presence of CaM and causes cell cycle arrest in vivo. Arrest is also accompanied by morphological defects. These results suggest the presence of a CaM-dependent protein kinase cascade in yeast and indicate that cmk1 may be important in cell cycle progression, a process known to be dependent on CaM in eukaryotic cells.

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Discovery of A Ca²⁺‐and calmodulin‐dependent protein phosphatase

Cited by 476 publications

References 21 publications

The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma

The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma

Redox Control of Calcineurin by Targeting the Binuclear Fe2+-Zn2+ Center at the Enzyme Active Site

Cloning of a Calmodulin Kinase I Homologue fromSchizosaccharomyces pombe

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Discovery of A Ca2+‐and calmodulin‐dependent protein phosphatase

Cited by 476 publications

References 21 publications

The Regulation of the Na+ ‐Ca2+ Exchanger of Heart Sarcolemma

The Regulation of the Na+ ‐Ca2+ Exchanger of Heart Sarcolemma

Redox Control of Calcineurin by Targeting the Binuclear Fe2+-Zn2+ Center at the Enzyme Active Site

Cloning of a Calmodulin Kinase I Homologue fromSchizosaccharomyces pombe

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Discovery of A Ca²⁺‐and calmodulin‐dependent protein phosphatase

The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma

The Regulation of the Na⁺ ‐Ca²⁺ Exchanger of Heart Sarcolemma