Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity

Stephen G. Miller, Bruce Patton, Mary B. Kennedy

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

After initial activation by Ca2+, the catalytic activity of type II Ca2+/calmodulin-dependent protein kinase rapidly becomes partially independent of Ca2+. The transition is caused by autophosphorylation of a few subunits in the dodecameric holoenzyme, which is composed of varying proportions of two homologous types of subunits, α (50 kd) and β (58-60 kd). We have identified one site in the α subunit (Thr286) and two in the β subunit (Thr287 and Thr382) that are rapidly autophosphorylated. We show that phosphorylation of α-Thr286 and β;-Thr287, which are located immediately adjacent to the calmodulin binding domain, controls Ca2+-independent activity. In contrast, phosphorylation of β-Thr382 is not required to maintain Ca2+ independence. It is absent in the a subunit and is selectively removed from the minor β subunit, apparently by alternative splicing. Regulation of the presence of β-Thr382 in the holoenzyme by both differential gene expression and alternative splicing suggests that it may have an important but highly specialized function.

Original languageEnglish (US)
Pages (from-to)593-604
Number of pages12
JournalNeuron
Volume1
Issue number7
DOIs
StatePublished - 1988
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Holoenzymes
Alternative Splicing
Phosphorylation
Calmodulin
Gene Expression

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity. / Miller, Stephen G.; Patton, Bruce; Kennedy, Mary B.

In: Neuron, Vol. 1, No. 7, 1988, p. 593-604.

Research output: Contribution to journalArticle

Miller, Stephen G. ; Patton, Bruce ; Kennedy, Mary B. / Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity. In: Neuron. 1988 ; Vol. 1, No. 7. pp. 593-604.
@article{43435ef2345b4ba8bd41dbf69ee7092f,
title = "Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity",
abstract = "After initial activation by Ca2+, the catalytic activity of type II Ca2+/calmodulin-dependent protein kinase rapidly becomes partially independent of Ca2+. The transition is caused by autophosphorylation of a few subunits in the dodecameric holoenzyme, which is composed of varying proportions of two homologous types of subunits, α (50 kd) and β (58-60 kd). We have identified one site in the α subunit (Thr286) and two in the β subunit (Thr287 and Thr382) that are rapidly autophosphorylated. We show that phosphorylation of α-Thr286 and β;-Thr287, which are located immediately adjacent to the calmodulin binding domain, controls Ca2+-independent activity. In contrast, phosphorylation of β-Thr382 is not required to maintain Ca2+ independence. It is absent in the a subunit and is selectively removed from the minor β subunit, apparently by alternative splicing. Regulation of the presence of β-Thr382 in the holoenzyme by both differential gene expression and alternative splicing suggests that it may have an important but highly specialized function.",
author = "Miller, {Stephen G.} and Bruce Patton and Kennedy, {Mary B.}",
year = "1988",
doi = "10.1016/0896-6273(88)90109-2",
language = "English (US)",
volume = "1",
pages = "593--604",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "7",

}

TY - JOUR

T1 - Sequences of autophosphorylation sites in neuronal type II CaM kinase that control Ca2+-independent activity

AU - Miller, Stephen G.

AU - Patton, Bruce

AU - Kennedy, Mary B.

PY - 1988

Y1 - 1988

N2 - After initial activation by Ca2+, the catalytic activity of type II Ca2+/calmodulin-dependent protein kinase rapidly becomes partially independent of Ca2+. The transition is caused by autophosphorylation of a few subunits in the dodecameric holoenzyme, which is composed of varying proportions of two homologous types of subunits, α (50 kd) and β (58-60 kd). We have identified one site in the α subunit (Thr286) and two in the β subunit (Thr287 and Thr382) that are rapidly autophosphorylated. We show that phosphorylation of α-Thr286 and β;-Thr287, which are located immediately adjacent to the calmodulin binding domain, controls Ca2+-independent activity. In contrast, phosphorylation of β-Thr382 is not required to maintain Ca2+ independence. It is absent in the a subunit and is selectively removed from the minor β subunit, apparently by alternative splicing. Regulation of the presence of β-Thr382 in the holoenzyme by both differential gene expression and alternative splicing suggests that it may have an important but highly specialized function.

AB - After initial activation by Ca2+, the catalytic activity of type II Ca2+/calmodulin-dependent protein kinase rapidly becomes partially independent of Ca2+. The transition is caused by autophosphorylation of a few subunits in the dodecameric holoenzyme, which is composed of varying proportions of two homologous types of subunits, α (50 kd) and β (58-60 kd). We have identified one site in the α subunit (Thr286) and two in the β subunit (Thr287 and Thr382) that are rapidly autophosphorylated. We show that phosphorylation of α-Thr286 and β;-Thr287, which are located immediately adjacent to the calmodulin binding domain, controls Ca2+-independent activity. In contrast, phosphorylation of β-Thr382 is not required to maintain Ca2+ independence. It is absent in the a subunit and is selectively removed from the minor β subunit, apparently by alternative splicing. Regulation of the presence of β-Thr382 in the holoenzyme by both differential gene expression and alternative splicing suggests that it may have an important but highly specialized function.

UR - http://www.scopus.com/inward/record.url?scp=0024073790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024073790&partnerID=8YFLogxK

U2 - 10.1016/0896-6273(88)90109-2

DO - 10.1016/0896-6273(88)90109-2

M3 - Article

C2 - 2856100

AN - SCOPUS:0024073790

VL - 1

SP - 593

EP - 604

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 7

ER -