Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

Article Details

Citation

Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M

Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007.

PubMed ID
18691976 [ View in PubMed
]
Abstract

Protein kinases are pivotal regulators of cell signaling that modulate each other's functions and activities through site-specific phosphorylation events. These key regulatory modifications have not been studied comprehensively, because low cellular abundance of kinases has resulted in their underrepresentation in previous phosphoproteome studies. Here, we combine kinase-selective affinity purification with quantitative mass spectrometry to analyze the cell-cycle regulation of protein kinases. This proteomics approach enabled us to quantify 219 protein kinases from S and M phase-arrested human cancer cells. We identified more than 1000 phosphorylation sites on protein kinases. Intriguingly, half of all kinase phosphopeptides were upregulated in mitosis. Our data reveal numerous unknown M phase-induced phosphorylation sites on kinases with established mitotic functions. We also find potential phosphorylation networks involving many protein kinases not previously implicated in mitotic progression. These results provide a vastly extended knowledge base for functional studies on kinases and their regulation through site-specific phosphorylation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Tyrosine-protein kinase ABL1P00519Details
NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrialP56181Details
Cystine/glutamate transporterQ9UPY5Details
7-dehydrocholesterol reductaseQ9UBM7Details
RAF proto-oncogene serine/threonine-protein kinaseP04049Details
Phenylalanine--tRNA ligase alpha subunitQ9Y285Details
Pyridoxal kinaseO00764Details
Pyruvate kinase PKMP14618Details
Monocarboxylate transporter 7O15403Details
Bifunctional glutamate/proline--tRNA ligaseP07814Details
Large neutral amino acids transporter small subunit 1Q01650Details
5'-AMP-activated protein kinase subunit beta-1Q9Y478Details
Sodium- and chloride-dependent creatine transporter 1P48029Details
Serine/threonine-protein kinase A-RafP10398Details
Abelson tyrosine-protein kinase 2P42684Details
Histamine H1 receptorP35367Details
Monocarboxylate transporter 4O15427Details
Receptor tyrosine-protein kinase erbB-2P04626Details
Chromodomain-helicase-DNA-binding protein 1O14646Details
Methionine--tRNA ligase, cytoplasmicP56192Details
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialP08559Details
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9Q9Y6M9Details
Tyrosine-protein phosphatase non-receptor type 1P18031Details
ADP/ATP translocase 3P12236Details
Acetyl-CoA carboxylase 1Q13085Details
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10AQ9Y233Details
Serine/threonine-protein kinase B-rafP15056Details
Monocarboxylate transporter 1P53985Details
5'-AMP-activated protein kinase catalytic subunit alpha-1Q13131Details
Retinoic acid-induced protein 3Q8NFJ5Details
DNA topoisomerase 2-alphaP11388Details
Epidermal growth factor receptorP00533Details
Activated CDC42 kinase 1Q07912Details
5'-AMP-activated protein kinase subunit beta-2O43741Details
Sphingosine-1-phosphate lyase 1O95470Details
Multidrug resistance-associated protein 1P33527Details
Glucocorticoid receptorP04150Details
Proto-oncogene tyrosine-protein kinase SrcP12931Details
Tyrosine-protein kinase FynP06241Details
Tyrosine-protein kinase YesP07947Details
Ephrin type-A receptor 2P29317Details
Tyrosine-protein kinase LckP06239Details
Insulin-like growth factor 1 receptorP08069Details
Dual specificity mitogen-activated protein kinase kinase 1Q02750Details
Protein-tyrosine kinase 2-betaQ14289Details
CTP synthase 1P17812Details
Cyclin-dependent-like kinase 5Q00535Details
Signal transducer and activator of transcription 5BP51692Details
Hepatocyte growth factor receptorP08581Details
Mitogen-activated protein kinase 1P28482Details
Apoptosis-inducing factor 1, mitochondrialO95831Details
Aurora kinase AO14965Details
CalnexinP27824Details
Rho-associated protein kinase 1Q13464Details
Mitogen-activated protein kinase 14Q16539Details
Proton-coupled folate transporterQ96NT5Details
Solute carrier family 2, facilitated glucose transporter member 1P11166Details
Mitogen-activated protein kinase 3P27361Details
Glycogen synthase kinase-3 betaP49841Details
Canalicular multispecific organic anion transporter 1Q92887Details
Cyclin-dependent kinase 2P24941Details
Cyclin-dependent kinase 1P06493Details
Long-chain-fatty-acid--CoA ligase 3O95573Details
Phosphatidylserine synthase 1P48651Details
CD44 antigenP16070Details
Heat shock protein HSP 90-alphaP07900Details
Protein kinase C alpha typeP17252Details
Inhibitor of nuclear factor kappa-B kinase subunit betaO14920Details
14-3-3 protein zeta/deltaP63104Details
Casein kinase II subunit alphaP68400Details
Protein kinase C theta typeQ04759Details
Tubulin alpha-1C chainQ9BQE3Details
Tubulin alpha-4A chainP68366Details
Uridine-cytidine kinase 2Q9BZX2Details
Dual specificity protein kinase CLK1P49759Details
TGF-beta receptor type-2P37173Details
Cyclin-dependent kinase 7P50613Details
Keratin, type II cytoskeletal 8P05787Details
Choline/ethanolaminephosphotransferase 1Q9Y6K0Details
Cyclin-dependent kinase 9P50750Details
Multifunctional protein ADE2P22234Details
CAD proteinP27708Details
Phosphatidylserine synthase 2Q9BVG9Details
Sphingomyelin phosphodiesterase 4Q9NXE4Details
Histone deacetylase 1Q13547Details
Histone deacetylase 2Q92769Details
DNA-dependent protein kinase catalytic subunitP78527Details
Serine/threonine-protein kinase mTORP42345Details
NF-kappa-B essential modulatorQ9Y6K9Details
Protein kinase C delta typeQ05655Details
Ribonucleoside-diphosphate reductase subunit M2P31350Details
Ephrin type-B receptor 4P54760Details
Keratin, type II cytoskeletal 7P08729Details
E3 ubiquitin-protein ligase UBR4Q5T4S7Details
Voltage-dependent anion-selective channel protein 1P21796Details
Voltage-dependent anion-selective channel protein 2P45880Details
Prostaglandin E synthase 3Q15185Details
Deoxycytidine kinaseP27707Details
Focal adhesion kinase 1Q05397Details
Integrin beta-4P16144Details
Casein kinase I isoform gamma-2P78368Details
Wee1-like protein kinaseP30291Details
Serine/threonine-protein kinase Chk1O14757Details
Aurora kinase BQ96GD4Details
Baculoviral IAP repeat-containing protein 5O15392Details
cAMP-dependent protein kinase type II-alpha regulatory subunitP13861Details
cAMP-dependent protein kinase type I-alpha regulatory subunitP10644Details
Mitogen-activated protein kinase kinase kinase 1Q13233Details
Protein kinase C epsilon typeQ02156Details
Heat shock protein beta-1P04792Details
Signal transducer and activator of transcription 3P40763Details
Ribosome-binding protein 1Q9P2E9Details
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2P16615Details
Casein kinase I isoform epsilonP49674Details
Cation-independent mannose-6-phosphate receptorP11717Details
Solute carrier organic anion transporter family member 4A1Q96BD0Details
Matrix metalloproteinase-15P51511Details
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8AO60658Details
Phosphatidylinositol 3-kinase catalytic subunit type 3Q8NEB9Details
Cyclin-A2P20248Details
Nuclear receptor coactivator 2Q15596Details
Serine/threonine-protein kinase PLK1P53350Details
cAMP-dependent protein kinase catalytic subunit alphaP17612Details
Mitogen-activated protein kinase 8P45983Details
Dual specificity protein kinase TTKP33981Details
Serine/threonine-protein kinase Nek2P51955Details
Inner centromere proteinQ9NQS7Details
60S ribosomal protein L23P62829Details
60S ribosomal protein L19P84098Details
60S ribosomal protein L37P61927Details
60S ribosomal protein L11P62913Details
Protein kinase C iota typeP41743Details
Proteasome subunit alpha type-5P28066Details
Casein kinase I isoform gamma-3Q9Y6M4Details
Casein kinase II subunit alpha'P19784Details
Dual specificity tyrosine-phosphorylation-regulated kinase 1AQ13627Details
STE20-like serine/threonine-protein kinaseQ9H2G2Details
Dual specificity protein kinase CLK3P49761Details
Geranylgeranyl transferase type-2 subunit betaP53611Details
Cyclin-dependent kinase 16Q00536Details
Serine/threonine-protein kinase Sgk1O00141Details
Calcium/calmodulin-dependent protein kinase type II subunit deltaQ13557Details
Serine/threonine-protein kinase 26Q9P289Details
Non-receptor tyrosine-protein kinase TYK2P29597Details
Rho-associated protein kinase 2O75116Details
Ribosomal protein S6 kinase alpha-1Q15418Details
Tyrosine-protein kinase LynP07948Details
SRSF protein kinase 2P78362Details
Interleukin-1 receptor-associated kinase 4Q9NWZ3Details
Mediator of RNA polymerase II transcription subunit 1Q15648Details
Calcium/calmodulin-dependent protein kinase type II subunit gammaQ13555Details
Mothers against decapentaplegic homolog 2Q15796Details
VimentinP08670Details
Ephrin type-B receptor 2P29323Details
[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrialO14874Details
Transitional endoplasmic reticulum ATPaseP55072Details
FAD-linked sulfhydryl oxidase ALRP55789Details
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5O60264Details
Spectrin beta chain, non-erythrocytic 1Q01082Details
Ribosomal protein S6 kinase alpha-4O75676Details
Serine/threonine-protein kinase TAO2Q9UL54Details
Protein-tyrosine kinase 6Q13882Details
Tyrosine-protein kinase FRKP42685Details
Dual specificity mitogen-activated protein kinase kinase 2P36507Details
Mitogen-activated protein kinase kinase kinase 2Q9Y2U5Details
LIM domain kinase 1P53667Details
Serine-protein kinase ATMQ13315Details
Ribosomal protein S6 kinase alpha-3P51812Details
Protein kinase C zeta typeQ05513Details
Membrane-associated progesterone receptor component 1O00264Details
5'-AMP-activated protein kinase catalytic subunit alpha-2P54646Details
5'-AMP-activated protein kinase subunit gamma-1P54619Details
5'-AMP-activated protein kinase subunit gamma-2Q9UGJ0Details
Histone H1.4P10412Details
Solute carrier family 2, facilitated glucose transporter member 6Q9UGQ3Details
Casein kinase II subunit betaP67870Details
Mitogen-activated protein kinase kinase kinase MLTQ9NYL2Details
Heterogeneous nuclear ribonucleoproteins A2/B1P22626Details
Heterogeneous nuclear ribonucleoprotein HP31943Details
Heterogeneous nuclear ribonucleoprotein H3P31942Details
Hepatoma-derived growth factorP51858Details
HuntingtinP42858Details
Prohibitin-2Q99623Details
Beclin-1Q14457Details
Heterogeneous nuclear ribonucleoprotein FP52597Details
Heterogeneous nuclear ribonucleoprotein KP61978Details
Tumor protein D54O43399Details
14-3-3 protein thetaP27348Details
Chromobox protein homolog 5P45973Details
Keratin, type II cytoskeletal 1P04264Details
Keratin, type I cytoskeletal 10P13645Details
Keratin, type II cytoskeletal 2 epidermalP35908Details
DesmoplakinP15924Details
Keratin, type I cytoskeletal 14P02533Details
Far upstream element-binding protein 2Q92945Details
Filamin-AP21333Details
Heterogeneous nuclear ribonucleoprotein D0Q14103Details
NucleophosminP06748Details
60S ribosomal protein L14P50914Details
60S ribosomal protein L18Q07020Details
60S ribosomal protein L4P36578Details
40S ribosomal protein S13P62277Details
40S ribosomal protein S6P62753Details
40S ribosomal protein S9P46781Details
Survival motor neuron proteinB4DP61Details
Bone morphogenetic protein receptor type-2Q13873Details
Splicing factor 3B subunit 1O75533Details
Elongation of very long chain fatty acids protein 5Q9NYP7Details
Serine/threonine-protein kinase 24Q9Y6E0Details
Serine/threonine-protein kinase 3Q13188Details
Serine/threonine-protein kinase 33Q9BYT3Details
Serine/threonine-protein kinase TAO1Q7L7X3Details
Serine/threonine-protein kinase TAO3Q9H2K8Details
Serine/threonine-protein kinase TBK1Q9UHD2Details
Serine/threonine-protein kinase tousled-like 2Q86UE8Details
TRAF2 and NCK-interacting protein kinaseQ9UKE5Details
Non-receptor tyrosine-protein kinase TNK1Q13470Details
Serine/threonine-protein kinase ULK1O75385Details
Serine/threonine-protein kinase ULK3Q6PHR2Details
AP2-associated protein kinase 1Q2M2I8Details
Tyrosine-protein kinase receptor UFOP30530Details
BMP-2-inducible protein kinaseQ9NSY1Details
Calcium/calmodulin-dependent protein kinase kinase 1Q8N5S9Details
Calcium/calmodulin-dependent protein kinase kinase 2Q96RR4Details
Dual specificity protein kinase CLK2P49760Details
Dual specificity protein kinase CLK4Q9HAZ1Details
Casein kinase I isoform alphaP48729Details
Eukaryotic translation initiation factor 2-alpha kinase 1Q9BQI3Details
eIF-2-alpha kinase GCN2Q9P2K8Details
Tyrosine-protein kinase FerP16591Details
Cyclin-G-associated kinaseO14976Details
Glycogen synthase kinase-3 alphaP49840Details
Serine/threonine-protein kinase ICKQ9UPZ9Details
Interleukin-1 receptor-associated kinase 1P51617Details
Serine/threonine-protein kinase LATS1O95835Details
LIM domain kinase 2P53671Details
Dual specificity mitogen-activated protein kinase kinase 5Q13163Details
Mitogen-activated protein kinase kinase kinase 11Q16584Details
Mitogen-activated protein kinase kinase kinase 3Q99759Details
Mitogen-activated protein kinase kinase kinase 6O95382Details
Mitogen-activated protein kinase kinase kinase kinase 4O95819Details
Serine/threonine-protein kinase MARK1Q9P0L2Details
Serine/threonine-protein kinase MARK2Q7KZI7Details
MAP/microtubule affinity-regulating kinase 3P27448Details
Megakaryocyte-associated tyrosine-protein kinaseP42679Details
Maternal embryonic leucine zipper kinaseQ14680Details
Misshapen-like kinase 1Q8N4C8Details
MAP kinase-interacting serine/threonine-protein kinase 2Q9HBH9Details
Serine/threonine-protein kinase Nek1Q96PY6Details
Serine/threonine-protein kinase Nek9Q8TD19Details
Serine/threonine-protein kinase PAK 4O96013Details
Cyclin-dependent kinase 17Q00537Details
Phosphatidylinositol 5-phosphate 4-kinase type-2 betaP78356Details
Phosphatidylinositol 5-phosphate 4-kinase type-2 gammaQ8TBX8Details
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinaseQ99640Details
Serine/threonine-protein kinase N1Q16512Details
Serine/threonine-protein kinase N2Q16513Details
Serine/threonine-protein kinase PLK4O00444Details
Serine/threonine-protein kinase RIO2Q9BVS4Details
Receptor-interacting serine/threonine-protein kinase 2O43353Details
Serine/threonine-protein kinase 10O94804Details
Histone-lysine N-methyltransferase EZH2Q15910Details
Exportin-1O14980Details
ATP-citrate synthaseP53396Details
Sodium-coupled neutral amino acid transporter 1Q9H2H9Details
Zinc transporter ZIP10Q9ULF5Details
Zinc transporter 5Q8TAD4Details
Zinc transporter ZIP3Q9BRY0Details
Zinc transporter 6Q6NXT4Details
V-type proton ATPase subunit HQ9UI12Details
Molybdopterin synthase catalytic subunitO96007Details
Receptor protein-tyrosine kinaseQ504U8Details
Serine/threonine-protein kinase ATRQ13535Details
Lysine-specific histone demethylase 1AO60341Details