A brain-specific Ca sup 2+ /calmodulin-dependent protein kinase (CaM kinase-Gr) is regulated by autophosphorylation. Relevance to neuronal Ca sup 2+ signaling

Journal Article · Sat Jun 15 00:00:00 EDT 1991 · Journal of Biological Chemistry; (United States)

OSTI ID:5510068

Frangakis, M V; Ohmstede, C A; Sahyoun, N ^[1]

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1. Wellcome Research Laboratories, Research Triangle Park, North Carolina (USA)

A neuronal Ca2+/calmodulin-dependent protein kinase (CaM kinase-Gr) undergoes autophosphorylation on a serine residue(s) in response to Ca2+ and calmodulin. Phosphate incorporation leads to the formation of a Ca(2+)-independent (autonomous) activity state, as well as potentiation of the Ca2+/calmodulin-dependent response. The autonomous enzyme activity of the phosphorylated enzyme {approximately} equals the Ca2+/calmodulin-stimulated activity of the unphosphorylated enzyme, but displays diminished affinity toward ATP and the synthetic substrate, syntide-2. The Km(app) for ATP and syntide-2 increased 4.3- and 1.7-fold, respectively. Further activation of the autonomous enzyme by Ca2+/calmodulin yields a marked increase in the affinity for ATP and peptide substrate such that the Km(app) for ATP and syntide-2 decreased by 14- and 8-fold, respectively. Both autophosphorylation and the addition of Ca2+/calmodulin are required to produce the maximum level of enzyme activation and to increase substrate affinity. Unlike Ca2+/calmodulin-dependent protein kinase type II that is dephosphorylated by the Mg(2+)-independent phosphoprotein phosphatases 1 and 2A, CaM kinase-Gr is dephosphorylated by a Mg(2+)-dependent phosphoprotein phosphatase that may be related to the type 2C enzyme. Dephosphorylation of CaM kinase-Gr reverses the effects of autophosphorylation on enzyme activity. A comparison between the autophosphorylation and dephosphorylation reactions of CaM kinase-Gr and Ca2+/calmodulin-dependent protein kinase type II provides useful insights into the operation of Ca(2+)-sensitive molecular switches.

• OSTI ID: 5510068
• Journal Information: Journal of Biological Chemistry; (United States), Vol. 266:17; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CALCIUM COMPOUNDS
BIOCHEMICAL REACTION KINETICS
CALMODULIN
PHOSPHOTRANSFERASES
PHOSPHORYLATION
AMINO ACIDS
ATP
AUTORADIOGRAPHY
BRAIN
ENZYME ACTIVITY
HOMEOSTASIS
MOLECULAR WEIGHT
NERVE CELLS
PHOSPHORUS ISOTOPES
RATS
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
ENZYMES
ISOTOPES
KINETICS
MAMMALS
NERVOUS SYSTEM
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
REACTION KINETICS
RODENTS
SOMATIC CELLS
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques