Thr286
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Home > Phosphorylation Site Page: > Thr286  -  CAMK2A (rat)

Site Information
sCMHRQEtVDCLkkF   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447797

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 23 , 49 , 51 , 53 ) , flow cytometry ( 4 ) , mass spectrometry ( 8 ) , mass spectrometry (in vitro) ( 16 ) , mutation of modification site ( 4 , 11 , 12 , 14 , 15 , 17 , 24 , 27 , 32 , 35 , 36 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 9 , 10 , 11 , 17 , 18 , 19 , 21 , 22 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 51 ) , phosphoamino acid analysis ( 23 , 49 ) , phosphopeptide mapping ( 23 , 49 , 51 , 53 ) , western blotting ( 1 , 2 , 3 , 4 , 9 , 10 , 15 , 18 , 21 , 22 , 27 , 28 , 31 , 32 , 34 , 35 , 36 , 37 , 41 , 42 , 43 , 44 , 51 )
Disease tissue studied:
adrenal cancer ( 42 ) , pheochromocytoma ( 42 ) , breast cancer ( 4 ) , neuroblastoma ( 4 )
Relevant cell line - cell type - tissue:
'brain, cerebellum' ( 25 ) , 'brain, cerebral cortex' ( 8 , 25 ) , 'brain, hippocampus' ( 1 , 19 , 22 , 25 , 31 , 34 , 39 , 40 , 41 , 44 , 45 , 46 , 51 , 53 ) , 'brain, nucleus accumbens' ( 21 ) , 'brain, striatum' ( 33 ) , 'muscle, skeletal' ( 10 ) , 'neuron, bipolar' ( 29 ) , 'neuron, cortical' ( 9 ) , 'neuron, hippocampal'-'brain, embryonic' ( 9 ) , 'neuron, hippocampal'-brain ( 24 , 37 ) , 'neuron, hippocampal, CA1 pyramidal'-brain ( 23 , 49 ) , 293 (epithelial) ( 15 , 32 ) , brain ( 18 , 43 ) , COS (fibroblast) ( 24 , 51 ) , dorsal root ganglia ( 26 ) , HeLa (cervical) ( 35 ) , MDA-MB-231 (breast cell) ( 4 ) , mesangial ( 36 ) , muscle ( 8 ) , myocyte-heart ( 2 ) , neuron-'brain, cerebral cortex' ( 27 ) , neuron-'brain, hippocampus' ( 11 , 12 , 13 , 14 , 15 , 28 , 32 , 35 , 38 ) , neuron:synaptosome-brain ( 17 ) , oligodendrocyte precursor ( 3 ) , PC-12 (chromaffin) ( 42 ) , SH-SY5Y (neural crest) ( 4 ) , spleen ( 8 ) , thymus ( 8 )

Upstream Regulation
Regulatory protein:
CALB1 (rat) ( 28 ) , TRPV1 (rat) ( 29 )
Putative in vivo kinases:
CAMK2A (rat) ( 49 )
Kinases, in vitro:
CAMK2A (rat) ( 16 , 25 , 30 , 35 , 47 , 48 , 49 , 51 , 54 , 55 ) , CAMK2B (rat) ( 16 ) , PKCA (rat) ( 50 )
Putative upstream phosphatases:
PPP1CA (human) ( 4 )
Phosphatases, in vitro:
PPP1CA (rat) ( 20 ) , PPP2CA (rat) ( 20 )
Treatments:
1,25D ( 28 ) , 17-beta-estradiol ( 9 ) , 5-HT2_receptor_agonists ( 27 ) , adenosine ( 45 ) , APV ( 31 , 34 , 41 ) , blast-induced traumatic brain injury ( 1 ) , bradykinin ( 42 ) , Ca(2+) ( 17 , 23 , 32 , 49 , 51 ) , caffeine ( 10 ) , calmodulin ( 17 ) , capsaicin ( 26 , 29 ) , carbachol ( 27 ) , cocaine ( 21 ) , depolarization ( 25 , 42 ) , dextromethorphan ( 39 ) , DNQX ( 39 ) , dopamine_depletion ( 33 ) , EGTA ( 51 , 53 ) , electrical_stimulation ( 45 ) , estradiol ( 18 ) , glutamic acid ( 3 , 27 , 35 , 42 ) , gly-aCSF ( 1 ) , GRGDSP ( 41 ) , H-7 ( 46 ) , heparin sodium ( 36 ) , ionomycin ( 36 ) , ischemia ( 22 , 39 , 43 , 44 ) , ischemia/reperfusion ( 19 , 38 , 40 , 43 , 44 ) , KN-62 ( 28 , 39 ) , KN-93 ( 34 ) , learning ( 31 ) , levodopa ( 33 ) , long-term_potentiation ( 34 , 45 ) , NGF ( 42 ) , nicotine ( 42 ) , nifedipine ( 39 ) , NMDA ( 11 , 34 , 45 ) , okadaic_acid ( 45 ) , PD168077 ( 27 ) , phorbol_ester ( 46 ) , PP2 ( 41 ) , progesterone ( 18 ) , SCH_23390 ( 21 ) , serum ( 36 ) , ST101 ( 7 ) , status epilepticus ( 19 ) , t-ACPD ( 46 ) , trifluoperazine ( 39 )

Downstream Regulation
Effects of modification on CAMK2A:
enzymatic activity, induced ( 17 , 29 , 36 , 49 ) , intracellular localization ( 11 , 15 , 22 , 38 ) , molecular association, regulation ( 15 , 17 , 23 , 24 , 32 ) , phosphorylation ( 23 , 48 ) , protein conformation ( 35 )
Effects of modification on biological processes:
cell growth, induced ( 4 ) , cytoskeletal reorganization ( 12 )
Induce interaction with:
CAMK2A (human) ( 48 ) , CAMK2A (rat) ( 23 , 49 ) , CAMK2B (rat) ( 23 , 49 ) , Calmodulin (human) ( 48 ) , DRD3 (rat) ( 17 ) , MARCKS (rat) ( 23 ) , NMDAR2A (human) ( 24 ) , NMDAR2B (human) ( 24 ) , RPT6 (rat) ( 15 ) , SYN1 (rat) ( 23 )
Inhibit interaction with:
CAMK2A (rat) ( 32 )

Disease / Diagnostics Relevance
Relevant diseases:
type 2 diabetes ( 5 ) , ischemia ( 39 )

References 

1

Vogel EW, et al. (2017) Primary Blast Injury Depressed Hippocampal Long-Term Potentiation through Disruption of Synaptic Proteins. J Neurotrauma 34, 1063-1073
27573357   Curated Info

2

Liu GS, et al. (2015) A novel human R25C-phospholamban mutation is associated with super-inhibition of calcium cycling and ventricular arrhythmia. Cardiovasc Res 107, 164-74
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3

Martinez-Lozada Z, et al. (2014) Activation of sodium-dependent glutamate transporters regulates the morphological aspects of oligodendrocyte maturation via signaling through calcium/calmodulin-dependent kinase IIβ's actin-binding/-stabilizing domain. Glia 62, 1543-58
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4

Hoffman A, et al. (2014) Dephosphorylation of CaMKII at T253 controls the metaphase-anaphase transition. Cell Signal 26, 748-56
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5

Liao MH, et al. (2013) The Disturbance of Hippocampal CaMKII/PKA/PKC Phosphorylation in Early Experimental Diabetes Mellitus. CNS Neurosci Ther 19, 329-36
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6

Robison AJ, et al. (2013) Behavioral and structural responses to chronic cocaine require a feedforward loop involving ΔFosB and calcium/calmodulin-dependent protein kinase II in the nucleus accumbens shell. J Neurosci 33, 4295-307
23467346   Curated Info

7

Moriguchi S, et al. (2012) The T-type voltage-gated calcium channel as a molecular target of the novel cognitive enhancer ST101: enhancement of long-term potentiation and CaMKII autophosphorylation in rat cortical slices. J Neurochem 121, 44-53
22251222   Curated Info

8

Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876
22673903   Curated Info

9

Logan SM, Sarkar SN, Zhang Z, Simpkins JW (2011) Estrogen-induced signaling attenuates soluble Aβ peptide-mediated dysfunction of pathways in synaptic plasticity. Brain Res 1383, 1-12
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10

Egawa T, et al. (2011) Caffeine activates preferentially α1-isoform of 5'AMP-activated protein kinase in rat skeletal muscle. Acta Physiol (Oxf) 201, 227-38
21241457   Curated Info

11

Marsden KC, Shemesh A, Bayer KU, Carroll RC (2010) Selective translocation of Ca2+/calmodulin protein kinase IIalpha (CaMKIIalpha) to inhibitory synapses. Proc Natl Acad Sci U S A 107, 20559-64
21059908   Curated Info

12

Pi HJ, et al. (2010) CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action. Proc Natl Acad Sci U S A 107, 14437-42
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13

Opazo P, et al. (2010) CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron 67, 239-52
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14

Pi HJ, et al. (2010) Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation. J Neurosci 30, 8704-9
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15

Bingol B, et al. (2010) Autophosphorylated CaMKIIalpha acts as a scaffold to recruit proteasomes to dendritic spines. Cell 140, 567-78
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16

Dosemeci A, Jaffe H (2010) Regulation of phosphorylation at the postsynaptic density during different activity states of Ca2+/calmodulin-dependent protein kinase II. Biochem Biophys Res Commun 391, 78-84
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17

Liu XY, et al. (2009) Activity-dependent modulation of limbic dopamine D3 receptors by CaMKII. Neuron 61, 425-38
19217379   Curated Info

18

Balasubramanian B, et al. (2008) Nonclassical Mechanisms of Progesterone Action in the Brain: II. Role of Calmodulin-Dependent Protein Kinase II in Progesterone-Mediated Signaling in the Hypothalamus of Female Rats. Endocrinology 149, 5518-26
18617607   Curated Info

19

Gurd JW, et al. (2008) Ischemia and status epilepitcus result in enhanced phosphorylation of calcium and calmodulin-stimulated protein kinase II on threonine 253. Brain Res 1218, 158-65
18514171   Curated Info

20

Brown AM, Baucum AJ, Bass MA, Colbran RJ (2008) Association of protein phosphatase 1 gamma 1 with spinophilin suppresses phosphatase activity in a Parkinson disease model. J Biol Chem 283, 14286-94
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21

Anderson SM, et al. (2008) CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking. Nat Neurosci 11, 344-53
18278040   Curated Info

22

Davies KD, Alvestad RM, Coultrap SJ, Browning MD (2007) alphaCaMKII autophosphorylation levels differ depending on subcellular localization. Brain Res 1158, 39-49
17559813   Curated Info

23

Avramovich-Tirosh Y, et al. (2007) Therapeutic targets and potential of the novel brain- permeable multifunctional iron chelator-monoamine oxidase inhibitor drug, M-30, for the treatment of Alzheimer's disease. J Neurochem 100, 490-502
17144902   Curated Info

24

Gardoni F, Polli F, Cattabeni F, Di Luca M (2006) Calcium-calmodulin-dependent protein kinase II phosphorylation modulates PSD-95 binding to NMDA receptors. Eur J Neurosci 24, 2694-704
17156196   Curated Info

25

Migues PV, et al. (2006) Phosphorylation of CaMKII at Thr253 occurs in vivo and enhances binding to isolated postsynaptic densities. J Neurochem 98, 289-99
16805815   Curated Info

26

Larsson M, Broman J (2006) Pathway-specific bidirectional regulation of Ca2+/calmodulin-dependent protein kinase II at spinal nociceptive synapses after acute noxious stimulation. J Neurosci 26, 4198-205
16624940   Curated Info

27

Gu Z, Jiang Q, Yuen EY, Yan Z (2006) Activation of dopamine D4 receptors induces synaptic translocation of Ca2+/calmodulin-dependent protein kinase II in cultured prefrontal cortical neurons. Mol Pharmacol 69, 813-22
16365279   Curated Info

28

Kim JH, et al. (2006) Overexpression of calbindin-D28K in hippocampal progenitor cells increases neuronal differentiation and neurite outgrowth. FASEB J 20, 109-11
16278289   Curated Info

29

Price TJ, Jeske NA, Flores CM, Hargreaves KM (2005) Pharmacological interactions between calcium/calmodulin-dependent kinase II alpha and TRPV1 receptors in rat trigeminal sensory neurons. Neurosci Lett 389, 94-8
16095822   Curated Info

30

Robison AJ, et al. (2005) Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. J Biol Chem 280, 35329-36
16120608   Curated Info

31

Bevilaqua LR, Medina JH, Izquierdo I, Cammarota M (2005) Memory consolidation induces N-methyl-D-aspartic acid-receptor- and Ca2+/calmodulin-dependent protein kinase II-dependent modifications in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor properties. Neuroscience 136, 397-403
16182449   Curated Info

32

Hudmon A, et al. (2005) A mechanism for Ca2+/calmodulin-dependent protein kinase II clustering at synaptic and nonsynaptic sites based on self-association. J Neurosci 25, 6971-83
16049173   Curated Info

33

Brown AM, Deutch AY, Colbran RJ (2005) Dopamine depletion alters phosphorylation of striatal proteins in a model of Parkinsonism. Eur J Neurosci 22, 247-56
16029214   Curated Info

34

Atkins CM, et al. (2005) Bidirectional regulation of cytoplasmic polyadenylation element-binding protein phosphorylation by Ca2+/calmodulin-dependent protein kinase II and protein phosphatase 1 during hippocampal long-term potentiation. J Neurosci 25, 5604-10
15944388   Curated Info

35

Takao K, et al. (2005) Visualization of synaptic Ca2+ /calmodulin-dependent protein kinase II activity in living neurons. J Neurosci 25, 3107-12
15788767   Curated Info

36

Xiao W, Liu Y, Templeton DM (2005) Ca(2+)/calmodulin-dependent protein kinase II inhibition by heparin in mesangial cells. Am J Physiol Renal Physiol 288, F142-9
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37

Zhao D, Watson JB, Xie CW (2004) Amyloid beta prevents activation of calcium/calmodulin-dependent protein kinase II and AMPA receptor phosphorylation during hippocampal long-term potentiation. J Neurophysiol 92, 2853-8
15212428   Curated Info

38

Tang K, Liu C, Kuluz J, Hu B (2004) Alterations of CaMKII after hypoxia-ischemia during brain development. J Neurochem 91, 429-37
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39

Fu XZ, Zhang QG, Meng FJ, Zhang GY (2004) NMDA receptor-mediated immediate Ser831 phosphorylation of GluR1 through CaMKIIalpha in rat hippocampus during early global ischemia. Neurosci Res 48, 85-91
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40

Takagi Y, et al. (2003) Transient global ischemia enhances phosphorylation of the GluR1 subunit of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor in the hippocampal CA1 region in rats. Neurosci Lett 341, 33-6
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41

Kramár EA, Bernard JA, Gall CM, Lynch G (2003) Integrins modulate fast excitatory transmission at hippocampal synapses. J Biol Chem 278, 10722-30
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42

Sakurada K, et al. (2002) Synapsin I is phosphorylated at Ser603 by p21-activated kinases (PAKs) in vitro and in PC12 cells stimulated with bradykinin. J Biol Chem 277, 45473-9
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43

Matsumoto S, Shamloo M, Isshiki A, Wieloch T (2002) Persistent phosphorylation of synaptic proteins following middle cerebral artery occlusion. J Cereb Blood Flow Metab 22, 1107-13
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44

Osuka K, et al. (2002) Phosphorylation of neuronal nitric oxide synthase at Ser847 by CaM-KII in the hippocampus of rat brain after transient forebrain ischemia. J Cereb Blood Flow Metab 22, 1098-106
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45

Huang CC, Liang YC, Hsu KS (2001) Characterization of the mechanism underlying the reversal of long term potentiation by low frequency stimulation at hippocampal CA1 synapses. J Biol Chem 276, 48108-17
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46

Gardoni F, Bellone C, Cattabeni F, Di Luca M (2001) Protein kinase C activation modulates alpha-calmodulin kinase II binding to NR2A subunit of N-methyl-D-aspartate receptor complex. J Biol Chem 276, 7609-13
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47

Lengyel I, et al. (2000) Modulation of the phosphorylation and activity of calcium/calmodulin-dependent protein kinase II by zinc. J Neurochem 75, 594-605
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48

Rich RC, Schulman H (1998) Substrate-directed function of calmodulin in autophosphorylation of Ca2+/calmodulin-dependent protein kinase II. J Biol Chem 273, 28424-9
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49

Scholz WK, Palfrey HC (1998) Activation of Ca2+/calmodulin-dependent protein kinase II by extracellular calcium in cultured hippocampal pyramidal neurons. J Neurochem 71, 580-91
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50

Waxham MN, Aronowski J (1993) Ca2+/calmodulin-dependent protein kinase II is phosphorylated by protein kinase C in vitro. Biochemistry 32, 2923-30
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51

Patton BL, Molloy SS, Kennedy MB (1993) Autophosphorylation of type II CaM kinase in hippocampal neurons: localization of phospho- and dephosphokinase with complementary phosphorylation site-specific antibodies. Mol Biol Cell 4, 159-72
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52

Cruzalegui FH, et al. (1992) Regulation of intrasteric inhibition of the multifunctional calcium/calmodulin-dependent protein kinase. Proc Natl Acad Sci U S A 89, 12127-31
1334558   Curated Info

53

Molloy SS, Kennedy MB (1991) Autophosphorylation of type II Ca2+/calmodulin-dependent protein kinase in cultures of postnatal rat hippocampal slices. Proc Natl Acad Sci U S A 88, 4756-60
1647015   Curated Info

54

Ohsako S, et al. (1991) Role of threonine-286 as autophosphorylation site for appearance of Ca2(+)-independent activity of calmodulin-dependent protein kinase II alpha subunit. J Biochem (Tokyo) 109, 137-43
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55

Thiel G, et al. (1988) Ca2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity. Proc Natl Acad Sci U S A 85, 6337-41
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