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 04:00:00 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), Journal Name: Journal of Biological Chemistry; (United States) Vol. 266:17; ISSN 0021-9258; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

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