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Supplementary data Protein kinase C (PKC) isozymes and cancer Jeong-Hun Kang TABLE S1: Target protein substrates for PKCs and their phosphorylation sites. PKC isozymes a Target protein substrates Phosphorylation sites Supplementa ry references PKCs Adducin (α-adducin) Adducin (β-adducin) Ser-716 and Ser-726 Ser-703 and Ser-713 [1] [1] PKCs α-helical head domain of desmin Ser-12, Ser-29, Ser- 38, and Ser-56 [2] PKCs α 2A -adrenergic receptor Ser-232 [3] PKCs α3A integrin Ser-1042 [4] PKCs α4 subunit of α4β2 neuronal nicotinic receptors Thr-532/Ser-550 (in vitro/in vivo) [5, 6] PKCs α6A integrin subunit Ser-1041 [7, 8] PKCα α6-tubulin Ser-165 [9] PKCs Alzheimer β/A4 amyloid precursor protein Ser-655 [10, 11] PKCs Angiotensin II receptor (AT 1A ) Ser-331, Ser-338, and Ser-348 [12] PKCs Annexin I (also known as calpactin II, p35, or lipocortine I) Thr-24, Ser-27, Ser- 28, and Thr-41 (major phosphorylation site, [13, 14] 1

Transcript of downloads.hindawi.comdownloads.hindawi.com/archive/2014/231418.f1.docx · Web viewPhosphoprotein...

Supplementary data

Protein kinase C (PKC) isozymes and cancer

Jeong-Hun Kang

TABLE S1: Target protein substrates for PKCs and their phosphorylation sites.PKC isozymes a Target protein substrates Phosphorylation sites Supplementary

references

PKCs Adducin (α-adducin)

Adducin (β-adducin)

Ser-716 and Ser-726

Ser-703 and Ser-713

[1]

[1]

PKCs α-helical head domain of desmin Ser-12, Ser-29, Ser-38, and Ser-56 [2]

PKCs α2A-adrenergic receptor Ser-232 [3]

PKCs α3A integrin Ser-1042 [4]

PKCs α4 subunit of α4β2 neuronal nicotinic

receptors

Thr-532/Ser-550 (in vitro/in vivo) [5, 6]

PKCs α6A integrin subunit Ser-1041 [7, 8]

PKCα α6-tubulin Ser-165 [9]

PKCs Alzheimer β/A4 amyloid precursor

protein

Ser-655 [10, 11]

PKCs Angiotensin II receptor (AT1A) Ser-331, Ser-338, and Ser-348 [12]

PKCs Annexin I (also known as calpactin II,

p35, or lipocortine I)

Thr-24, Ser-27, Ser-28, and Thr-

41 (major phosphorylation site,

Ser-27 and Thr-41)

[13, 14]

PKCα, βΙ, and

βII

Annexin II (also known as calpactin I,

p36, or lipocortine II)

Ser-25 [15, 16]

cPKCs Annexin IV (also known as endonexin I

or p33/40)

Thr-6 [17]

cPKCs Avian retrovirus matrix protein Ser-68 and Ser-106 [18]

PKCθ and ε Bad (Bcl-associated death protein) Ser-112 [19]

PKCι Ser-112, Ser-136, and Ser-155 [20]

PKCs basic fibroblast growth factor (also Ser-64 [21]

1

known as bFGF, FGF2, or FGF-β)

PKCα Bcl-2 Ser-70 [22]

PKCδ Bcl-2 associated athanogene 3 (BAG3) Ser-187 [23]

PKCα β-catenin Ser-33, Ser-37, and Ser-45 [24]

PKCs β2-adrenergic receptor Ser-261, Ser-262, Ser-344, and

Ser-345

[25, 26]

PKCs β4 integrin subunit Ser-1360 [27]

PKCα β4 integrin subunit Ser-1360 and Ser-1364 [28]

PKCs BK channel (large Ca2+-activated

potassium channel)

Ser-695 and Ser-1151 [29]

PKCε Borna disease virus P-protein Ser-26 and Ser-28 [30]

PKCs Bradykinin B2 receptor Ser-346 [31]

PKCs Canonical transient receptor potential

channel subtype 3 (TRPC3)

TRPC5

TRPC6A

TRPC6B

Ser-712

Thr-972

Ser-748

Ser-714

[32]

[33]

[34]

[34]

PKCδ TRPC6 Ser-448 [35]

PKCs Cardiac myosin-binding protein C

(cMyBP-c) (also known as MYBPC3)

Ser-273 and Ser-302/Ser-265 and

Ser-300 (human/chicken)

[36, 37]

PKCs Ca2+/calmodulin-dependent protein

kinases II (CaM kinases II)

Thr-286 [38]

PKCs CD33 (known as Siglec-3) Ser-307 [39]

PKCs cGMP-dependent protein kinase (PKG or

cGK) 1α

Thr-58 [40]

PKCs Chaperone or modulatory protein 14-3-3 Ser-58, Ser-59, and Ser-60 for 14-

3-3ζ, 14-3-3η, and 14-3-3β,

respectively

[41]

cPKCs Choline acetyltransferase Thr-255, Ser-346, Ser-347, Ser-

440, and Ser-476

(nPKCs and aPKCs

phosphorylate Ser-440 and Ser-

476)

[42]

PKCα c-kit-encoded tyrosine kinase receptor

for stem cell factor (Kit/SCFR)

Ser-741 and Ser-746 [43]

PKCζ c-Myc Ser-373 [44]

2

PKCε Connexin 43 (Cx43) (also known as gap

junction α-1 protein)

Ser-262

Ser-368

[45]

[46]

PKCs CPI-17 (protein kinase C-dependent

inhibitory of 17 kDa)

Thr-38 [47]

PKCs CTP synthetase 1 Ser-462 and Thr-455 [48]

PKCγ

cPKCs

Diacylglycerol kinase (DGK)γ accessory

domain

DGKδ1 PH domain

Ser-776 and Ser-779

Ser-22 and Ser-26

[49]

[50]

PKCα Dynamin I Ser-795 [51]

PKCs Dystrophin Ser-136 and Ser-147 [52]

PKCα ELAV-like protein HuR (HuA) Ser-158 and Ser-221 [53]

PKCs Endothelial nitric oxide synthase (eNOS) Thr-495/497 (human/bovine) [54, 55]

PKCs Epidermal growth factor receptor

(EGFR)

Thr-654 [56, 57]

PKCι Epithelial cell transformaing sequence 2

(Ect2)

Thr-328 [58]

PKCδ ErbB3-binding protein 1 (EBP1) Ser-360 [59]

PKCδ

PKCβΙ

Eukaryotic elongation factor 1α (eEF-1α) Thr-431

Ser-53

[60]

[61]

PKCs Eukaryotic initiation factor-2β (eIF-2β)

eIF-2γ

eIF-4E

Ser-13

Thr-66

Ser-209 and Thr-210

[62]

[63]

[64]

PKCα Farnesoid X receptor (FXR) (also known

as NR1H4)

Ser-135 and Ser-154 [65]

PKCs Fms-interacting protein (FMIP) Ser-5 and Ser-6 [66]

PKCs γ-aminobutyric acid type A (GABAA)

receptor β1 subunit

GABAA receptor β2 subunit

GABAA receptor γ2S subunit

GABAA receptor γ2L subunit

Ser-409

Ser-410

Ser-327

Ser-343

[67]

[68]

[67, 68]

[67]

PKCs GluA1 AMPA receptor subunit Ser-831 [69, 70]

PKCα and γ Glutathione S-transferase P1 (GSTP1) Ser-42 and Ser-148 in the absence

of glutathione

[71]

PKCα, βI, βII,

γ, δ, ε, η, and ζ

Ser-42 and Ser-148 in the

presence of glutathione

3

PKCα, βII, γ, δ,

and η

(PKCβII and δ

are very weak)

Glycogen synthase kinase (GSK)-3α Ser-21 [72]

PKCα, βI, and γ GSK-3β Ser-9 [73]

PKCα, βI, and η Ser-9 [72]

PKCs G protein α subunit Gzα Ser-25 and Ser-27 [74]

PKCα, δ, and ζ G protein-coupled receptor kinase-2

(GRK2) [also known as β-adrenergic

receptor kinase (βARK)]

Ser-29 [75, 76]

PKCs GRK5 Ser-566 and Ser-572 [77]

PKCα GTPase activating protein (GAP) p190A Ser-1221 and Thr-1226 [78]

PKCs GTP-binding protein γ12 Ser-1 [79]

PKCδ Heat-shock protein-25/27 Ser-15 and Ser-86 [80]

PKCs Hepatitis B virus surface M protein (C-

termimally truncated middle size protein)

Ser-28 [81]

PKCs Hepatitis C virus core protein Ser-116 [82]

PKCs Hepatocyte growth factor receptor kinase Ser-985 [83]

PKCζ Heterogeneous ribonuscleoprotein A1 Ser-199 + three unknown sites [84]

cPKCs and

PKCδ

High-mobility-group protein-1 Ser-44 and Ser-64 [85]

PKCs Histamin H1 receptor (H1R) Ser-398 [86]

PKCs Histone H1 Ser-103 [87]

PKCβΙ Histone H3 Thr-6 [88]

PKCε and β Ser-10 [89]

PKCs HIV-1 gag protein Ser-111 [90]

PKCδ HuR Ser-318 [91]

PKCε IKKβ Ser-177 [92]

PKCs Insulin receptor Thr-1336 [93]

PKCζ Insulin-responsive aminopeptidase

(IRAP)

Ser-80 and Ser-91 [94]

PKCδ

PKCθ

PKCβII

PKCδ

Insulin receptor substrate-1 (IRS-1)

(human)

IRS-1 (human)

IRS-1 (mouse)

Ser-24, Ser-307, Ser-323, and Ser-

574

Ser-1101

Ser-336

[95, 96]

[97]

[98]

[99]

4

PKCζ IRS-1 (rat)

IRS-1 (rat)

Ser 357

Ser-318, Ser-498, Ser-570, and

Ser-612 (major phosphorylation

site, Ser-318)

[100, 101]

PKCι Interleukin-1 receptor-associated kinase

(IRAK)

Thr-66 [102]

PKCs Interleukin-2 (IL-2) Ser-7 [103]

PKCs Iron-responsive element-binding protein Ser-138 and Ser-711 [104]

cPKCs Junctional adhesion molecule (JAM) Ser-284 [105]

PKCε Keratin 8 Ser-8 and Ser-23 [106]

PKCε Keratin 18 Ser-52 [107]

PKCδ and ε Kv3.1b potassium channel Ser-503 [108]

PKCα, βΙ, βII,

γ, δ, and θ

All PKCs

except PKCη

L-type Ca2+ channel (also known as

voltage-dependent Ca2+ channel or

Cav1.2 α1c)

Ser-1674

Ser-1928

[109]

[109, 110]

PKCs L-myc Ser 38 and Ser 42 [111]

PKCs Lens fiber major intrinsic protein Ser-245 [112]

PKCs Microtubule-associated protein 2

(MAP2)

MAP4

Ser-1703, Ser-1711, and Ser-1728

Ser-815

[113]

[114]

cPKCs Myelin basic protein (MBP) Ser-110 and Ser-115 [115]

PKCs Ser-8, Ser-11, Ser-46, Ser-55, Ser-

110, Ser-132, Ser-151, and Ser-

161

[116]

PKC βII Myristoylated alanin-rich kinase

substrate (MARCKS) (also known as

p80 and p87)

Ser-152 and Ser-156 (murine) [117]

PKCs Ser-45, Ser-80, Ser-99, and Ser-

116 (bovine)

Ser-152, Ser156, and Ser-163

(murine)

[118]

[119]

PKCs NADPH oxidase activator 1 (NOXA1) Ser-172 [120]

PKCζ

cPKCs

NADPH oxidase component p47phox Ser-303, Ser-304, and Ser-315

Ser-303, Ser-304, Ser-320, and

Ser-328

[121]

[122]

5

PKCs Na,K-ATPase α-subunit Ser-11 and Ser-18

Ser-774 and Thr-938

[123]

[124]

PKCs NAP-22 (also known as GAP-23 and

BASP1)

Ser-6 [125]

PKCθ NDRG2 (NDRG family member 2) Ser-332 [126]

PKCs Neurogranin (also known as p17,

BICKS, or RC3 protein)

Ser-36 [127, 128]

PKCs Neuronal growth-associated protein B-50

(also known as GAP-43, protein F1, p57,

pp46, or neuromodulin)

Ser-41 (mammals)/Ser-42 (chick)

Ser-209

[129, 130]

[131]

PKCα NG2 proteoglycan Thr-2256 [132]

PKCs N-methyl-D-aspartate (NMDA) receptor

1 subunit

Ser-890 and Ser-896 [133, 134]

PKCβII Nonmuscle myosin heavy chain IIA Ser-1917 [135]

PKCs Nonmuscle myosin heavy chain IIB Ser-362 and Ser-370/Ser-368 and

Ser-370 (βF47/αF47)

[136]

cPKCs

PKCβII

PKCα

Nuclear lamin (also known as class V

intermediate filament) A

Nuclear lamin B

Nuclear lamin C

Ser-5 and Ser-525

Ser-395 and Ser-405

Ser-572

[137]

[138, 139]

[140]

PKCs Nucleolar protein B23 (also known as

nucleophosmin, numatrin, or nucleolar

protein NO38)

Ser-225 [141]

PKCη Occludin Thr-403 and Thr-404 [142]

PKCs Opi1p Ser-26 [143]

aPKCs (PKCζ

and λ)

Par-1b kinase T595 [144, 145]

aPKCs Par-3 Ser-827 [146]

PKCs P-glycoprotein Ser-661 [147]

PKCs Phosphatidylinositol transfer protein (PI-

TP)α

Ser-166 [148]

PKCs Phosphodiesterase (PDE) 3A Ser-312, Ser-428, Ser-438, Ser-

465, and Ser-492

[149]

PKCζ 3-phosphoglycerate dehydrogenase

(PHGDH)

Ser-55, Thr-57, and Thr-78 [150]

6

PKCθ Phosphoinositide-dependent protein

kinase-1 (PDK1)

Ser-504 and Ser-532 [151]

PKCs Phospholemman (PLM) (also known as

FXYD1)

Ser-63 and Ser-68

Thr-69

[152]

[153]

PKCs Phospholipase D1 (PLD1) Ser-2, Thr-147, and Ser-561 [154]

PKCδ Phospholipid scramblase Thr-161 [155]

PKCs Phosphoprotein enriched in diabetes-15

(PED-15) [(also known as

phosphoprotein enriched in astrocytes

(PEA)-15]

Ser-104 [156]

PKCζ Phosphoprotein of human parainfluenza

virus type 3

Ser-333 [157]

PKCα, β, γ, and

ζ

Phosphoprotein of rabies virus Ser-162, Ser-210, and Ser-271 [158]

PKCs pp60src Ser-12 [159, 160]

PKCζ Profilin Ser-137 [161]

PKCs Protamine P1

Protamine P2 (stallion)

Ser-21 for human and Ser-29 for

stallion

Ser-32

[162, 163]

[162]

PKCα Protein interacting with C kinase 1

(PICK1)

Ser-77 [164]

PKCε and η/δ

PKCδ

Protein kinase D Ser-744 and Ser-748/Ser-738 and

Ser-742 (mouse/human)

Ser-412 (human)

[165, 166]

[167]

PKCs Protein phosphatase inhibitor-1 Ser-65 [168]

PKCs Protein tyrosine phosphate PTP-PEST Ser-39 and Ser-435 [169]

PKCs p120-catenin Ser-873 [170]

aPKCs (PKCζ) p21 [cyclin-dependent kinase (Cdk)

inhibitor]

Ser-146 [171]

PKCs Ser-153 [172]

PKCα

PKCδ

p53 tumor suppressor Ser-371 (human)

Ser-46

[173]

[174]

PKCs Ser-360, Thr-365, Ser-370, Thr-

371, Ser-372, and Thr-377

(mouse)

[175, 176]

PKCδ p73β (one of p53 homologs) Ser-289 [177]

7

PKCs Rad Ser-214, Ser-257, Ser-273, Ser-

290, and Ser-299

[178]

PKCα Raf-1 Ser-497 and Ser-499 [179]

PKCs Ser-497 and Ser-619 [180]

cPKCs and

aPKCs

Raf kinase inhibitory protein Ser-153 [181]

PKCθ

PKCθ

RasGRP2 (Ras guanine-releasing protein

2)

RasGRP3

Ser-960

Thr-133

[182]

[183]

PKCs Ras p21 (H-ras p21 and K-ras p21) Ser-177 for H-ras p21 and Ser

181 for K-ras p21

[184-186]

PKCs Receptor-like protein-tyrosine

phosphatase (RPTP)α

Ser-180 and Ser-204 [187]

PKCζ RelA Ser-311 [188]

PKCα Retinoic acid-related orphan nuclear

receptor (ROR)α

Ser-35 [189]

cPKCs Ribosomal protein S6 Ser-5, Ser-9, and Ser-11 [190]

PKCβΙ, βII, and

δ

Ribosomal protein S6 kinase (S6K) βII Ser-486 [191]

PKCε RhoA Thr-127 and Ser-188 [192]

PKCs Rhodopsin Ser-334 [193]

PKCα RLIP76 Thr-297 [194]

PKCs ROMK1 (also known as KIR1.1) Ser-4 and Ser-201 [195]

PKCs Seminal vesicle protein IV Ser-58 [196]

PKCs SM22 (also known as smooth muscle

protein 22 or transgelin)

Ser-181 [197]

PKCs Smooth muscle caldesmon Ser-127, Ser-587, Ser-600, Ser-

657, Ser-686, and Ser-726 (major

phosphorylation site, Ser-587 and

Ser-600)

[198, 199]

PKCs Smooth muscle myosin light chain Ser-1 and/or Ser-2 and Thr-9 [200, 201]

PKCζ Sp1 (specificity protein 1) Ser-641 [202]

PKCδ Stat3 (signal transducer and activator of

transcription 3)

Ser-727 [203]

PKCε Ser-727 [204]

8

PKCs Synaptosomal-associated protein of 25

kDa (SNAP-25)

Ser-187 [205]

PKCs Synaptotagmin Ι Thr-112 [206]

PKCs Syndecan cytoplasmic domain Ser-197 and Ser-339 [207]

PKCs Tac antigen (interleukin 2 receptor) Ser-247 and Ser-250 [208]

PKCs Talin (cytoskeletal protein) Thr-144, Thr-150, and Ser-425 [209]

PKCs Tau (microtubule-associated proteins) Ser-293, Ser-305, and Ser-324 [210, 211]

PKCs Transcription factor C/EBP

(CCAAT/enhancer-binding protein)

Ser-248 [212]

PKCε Transient receptor potential cation

channel subfamily V member 1 (TRPV1)

(known as capsaicin receptor or vanilloid

receptor)

Ser-800 [213]

PKCs Transferrin receptor Ser-24 [214]

PKCδ Troponin I (TnI) (bovine) Ser-23/Ser-24 [215]

PKCs Ser-43/45, Ser-78, and Thr-144 [216, 217]

PKCα, δ, and ε Troponin T (TnT) (bovine) Thr-190, Thr-194, Thr-199, and

Thr-280

[215]

PKCs Thr-190, Thr-199, and Thr-280

Thr-197, Ser-201, Thr-206, and

Thr-287 (functionally critical

phosphorylation site, Thr-206)

[216]

[218]

PKCε UDP-glucuronosyltransferase (UGT)

1A7

Ser-432 [219]

PKCs Vasodilator-stimulated phosphoprotein

(VASP)

Ser-157 [220]

PKCs Vimentin Ser-4, Ser-6, Ser-7, Ser-8, and

Ser-9

[221, 222]

PKCα Vinculin Ser-1033 and Ser-1045 [223]

PKCs Vitronectin Ser-362 [224]

PKCβ Vitamin D receptor Ser-51 [225]

PKCs Yeast choline kinase Ser-30 [226]a PKCs, unknown PKC isozymes; cPKCs, conventional or classic PKCs; and aPKCs, atypical PKCs.

9

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