Your browser doesn't support javascript.
loading
Activation State-Dependent Substrate Gating in Ca2+/Calmodulin-Dependent Protein Kinase II.
Johnson, D E; Hudmon, A.
Afiliación
  • Johnson DE; Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Hudmon A; Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Neural Plast ; 2017: 9601046, 2017.
Article en En | MEDLINE | ID: mdl-29391954
Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly concentrated in the brain where its activation by the Ca2+ sensor CaM, multivalent structure, and complex autoregulatory features make it an ideal translator of Ca2+ signals created by different patterns of neuronal activity. We provide direct evidence that graded levels of kinase activity and extent of T287 (T286α isoform) autophosphorylation drive changes in catalytic output and substrate selectivity. The catalytic domains of CaMKII phosphorylate purified PSDs much more effectively when tethered together in the holoenzyme versus individual subunits. Using multisubstrate SPOT arrays, high-affinity substrates are preferentially phosphorylated with limited subunit activity per holoenzyme, whereas multiple subunits or maximal subunit activation is required for intermediate- and low-affinity, weak substrates, respectively. Using a monomeric form of CaMKII to control T287 autophosphorylation, we demonstrate that increased Ca2+/CaM-dependent activity for all substrates tested, with the extent of weak, low-affinity substrate phosphorylation governed by the extent of T287 autophosphorylation. Our data suggest T287 autophosphorylation regulates substrate gating, an intrinsic property of the catalytic domain, which is amplified within the multivalent architecture of the CaMKII holoenzyme.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Dominio Catalítico / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Límite: Humans Idioma: En Revista: Neural Plast Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Dominio Catalítico / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Límite: Humans Idioma: En Revista: Neural Plast Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos