カルモジュリン依存性プロテインキナーゼ

シグナル伝達

Ca2+/カルモジュリン依存性プロテインキナーゼ、CaMキナーゼ
ホスホリラーゼキナーゼ、ミオシンL鎖キナーゼ、CAMK I〜IVに分類される。
Caイオンをセカンドメッセンジャーとする情報伝達に貢献するが、ホスホリラーゼキナーゼはプロテインキナーゼＡによるリン酸化による活性化を受ける。
CAMK IIは自己リン酸化により（CAMK I, CAMK IVは上流酵素CAMKKによるリン酸化により）持続的な活性化による細胞応答に関わる。

Calcium/calmodulin-dependent protein kinase type II subunit beta

Short name=CaM kinase II subunit beta
Short name=CaMK-II subunit beta
EC=2.7.11.17

Function
Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca2+/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca2+ transport in skeletal muscle. In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Participates in the modulation of skeletal muscle function in response to exercise. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca2+ transport and in fast-twitch muscle participates in the control of Ca2+ release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. Ref.11
Catalytic activity
ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation
Activated by Ca2+/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca2+-independent activity. Ref.9
Subunit structure
CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with SYNGAP1 and CAMK2N2 By similarity. Interacts with MPDZ. Ref.9 Ref.10
Subcellular location
Cytoplasm › cytoskeleton. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Sarcoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Note: In slow-twitch muscle, evenly distributed between longitudinal SR and junctional SR. Ref.13
Tissue specificity
Widely expressed. Expressed in adult and fetal brain. Expression is slightly lower in fetal brain. Expressed in skeletal muscle. Ref.11
Induction
Activity is induced in skeletal muscle during exercise. Ref.9 Ref.11
Domain
The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.
Post-translational modification
Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.

Sequence similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
Contains 1 protein kinase domain.


Calcium/calmodulin-dependent protein kinase kinase 1

Short name=CaM-KK 1
Short name=CaM-kinase kinase 1
Short name=CaMKK 1
EC=2.7.11.17
Alternative name(s):
CaM-kinase IV kinase
Calcium/calmodulin-dependent protein kinase kinase alpha
Short name=CaM-KK alpha
Short name=CaM-kinase kinase alpha
Short name=CaMKK alpha

Function
Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. Ref.4
Catalytic activity
ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation
Activated by Ca2+/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA By similarity. May be regulated through phosphorylation by CAMK1 and CAMK4.
Subunit structure
Interacts with CAMK4 and calmodulin By similarity.
Subcellular location
Cytoplasm By similarity. Nucleus By similarity.
Domain
The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric auto inhibition. The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates By similarity.
Post-translational modification
Appears to be autophosphorylated in a Ca2+/calmodulin-dependent manner. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to Ca2+/calmodulin. In vitro, phosphorylated by CAMK1 and CAMK4 By similarity.
Sequence similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain.