
protein phosphorylation

protein phosphorylation ennathu proteinukalude oru reversible poost-translation parishkkaranamaan, athil oru amino assid avashishtam oru protein kinace upayogichu phosphorylate cheiyunnu, koodaathe oru kovalanti boundu phoosphett group cherkkunnu. phosphorylation oru proteente gadanaaparamaaya roopeekaranathe maattunnu, ithu athu sajeevamaakukayo nirjjeevamaakkukayo allengil athinte pravartthanatthe parishkkarikkukayo cheiyunnu. ekadesham 13000 manushya proteinukalkku phosphorylated saittukalund.
phosphorylationte vipareeta prathikaranatthe defosphorylation ennu vilikkunnu, ithu protein phosphataseukal vazhi uthejippikkappedunnu. protein kainesukalum phosphataseukalum proteinukalude pravartthanam niyanthrikkunnathin swathanthramaayum santhulithamaayum pravartthikkunnu.
serin, thrionin, eukkaariyottukalile tyrosine, prokaariyottukalileyum sasyangalileyum histidin ennivayaanu ettavum saadhaaranayaayi phosphorylated amino aasidukal (ithu ippol manushyaril saadhaaranamaanennu ariyappedunnu). signalling paathakalilum mettabolisathilum eee phosphorilationukal pradhanavum nannayi savisheshathayullathumaaya punk vahikkunnu. ennirunnaalum, arjinin, lysine, aspartic assid, glutamic assid, sisttain ennivayulppede mattu amino aasidukalkk poost-translation aayi phosphorilettu cheyyaan kazhiyum, koodaathe eee phosphorylated amino aasidukal manushya koshangalude sathil undennu aduthide thiricharinjittundu.
1906ll rockfeller instittyoott phoor medical researchile phosphorylated vitalin kandethiyappol fobus leven aanu protein phosphorilation aadyamaayi report cheythath. ennirunnaalum, protein kainaasukal proteinukalude ensaimatik phosphorylation kandethunnathuvare ekadesham 50 varshamaayirunnu.
charithram.
1906ll rockfeller instittyoott phoor medical researchile fobus leven protein vittellinile (fosvittin) phoosphett thirichariyukayum 1933 aayappozhekkum fritts lipmanumaayi keysinil phosphoserine kandethukayum cheythu. ennirunnaalum, yujeen pii. kku munbu 20 varsham koodi vendivannu. aadyathe 'proteinukalude ensaimatik phosphorylation' kenneddy vivarichu. 1930kalude avasaanathil kaal, jerty koorii ennivar chernnaanu aadyathe phosphorylase ensime kandethiyathu. carle jerty koriyum glycojan phosphorilesinte rund roopangal kandethi, avaykku avar eiii, bii ennu perittu, pakshe bii roopathinte oru roopa parivarthanatthinulla samvidaanam shariyaayi manassilakkiyilla. phosphorylase bii-yude phosphorylase eiii-yilekkulla paraspara parivartthanatthe pinneedu edmund fisher edwin crebukalum vivarichu, athupole thanne phosphorilation/defosphorilation samvidaanam ulppedunna vosilaittum sna. phosphorylase bii yill oru serin avashishtathilekku eiii. tii. piyude γ-phosphoril groupine kaimaran sahaayikkunnathiloode glycojan phosphorilesinu phosphorylase kinace, emji-eiii. tii. pii. ennee ensimeukal aavasyamaanennu kandethi. phoosphett groupine neekkam cheythukondu phosphorylated ensaimukalude defosphorylation uthejippikkaan protein phosphatase 1 nuu kazhiyum. 1950ll phosphorilesinte pravartthanam vardhichuvennum karal kashanagal adrenaline, glookagan enniva upayogichu incubate cheyyumbol glycogenolysis uthejippichuvennum erl vishadeekarichu. 1970kalil mitocondrial pairuvettu dehydrogenase complexes phosphorylation vazhi nirjjeevamakkiyathaayi lesttar reed kandethunnathuvare phosphorylation oru upapachayam paathaykkulla oru prathyeka niyanthrana samvidaanamaayi kanakkaakkappettirunnu. rando athiladhikamo avashishtangalil rando athiladhikamo kainaasukal phosphorylate cheytha proteinukalude kandethalinodu prathikarichaanu 1970-kalil multicite phosphorylation enna padam upayogichathu. 1975ll, camp-ashrita proteinukal phosphorilettu serin avashishtangale nirddishta amino assid sequence roopangalil kainas cheiyunnuvennu kaanichu. vii-src oru kinace aanennu reey eriksan kandethi, tonny vettakkaaran 1970 kalil proteinukalil vii-src phosphorylated tyrosine avashishtangal kandethi. 1980-nte thudakkathil, aadyathe protein kainesinte amino assid shreni nirnnayichu, ithu janithakashaasthranjare regulatory jeenukalude pravartthanangal manasilakkaan sahayichu. 1980kalude avasaanathilum 1990kalude thudakkathilum aadyathe protein tyrosine phosphatase (pidipi1bii) shudheekarikkappedukayum jacq kainaasukalude cloning nadathukayum cheythu, ithu 1990kalle protein kainas kaaskedukalude dasakamaayi namakaranam cheyyaan shaasthra samoohathile palareyum prerippichu. oru jaiva niyanthrana samvidaanamenna nilayil reversible protein phosphorylationecurichlu kandethalukalkk" 1992-ll edmund fisher, edwin crebs ennivarkku nobal sammanam labhichu.
samriddham.
proteinukalude reversible phosphorylation procariottikkilum athilum kooduthal eucariotic jeevikalilum daaraalamundu. udaaharanathinu, bakteeriyakalil ellah proteinukalilum 5-10% phosphorylated aanennu karuthappedunnu. ithinu vipareethamaayi, manushya proteinukalude moonnilonnu eathu samayathum phosphorylated aanennu kanakkaakkappedunnu, yathaakramam 230,000,156,000,4,000 advitheeya phosphorylation sittukal manushyarilum elikalilum yeesttilum undu. yeesttil, ekadesham 120 kainaasukal (motham 6000 proteinukalil) 8814 ariyappedunna niyantritha phosphorylation sambhavangalkk kaaranamaakunnu, ithu ekadesham 3,600 phosphoproteinukal (ellah yeest proteinukaludeyum ekadesham 60 sathamaanam) uthpaadippikkunnu. athinaal, proteinukalude valiyoru bhaagathe badhikkunna oru saarvathrika niyanthrana samvidaanamaanu phosphorylation. oru protein svayam phosphorylated allengilum, mattu proteinukalumaayulla athinte edapedalukal eee prathipravartthikkunna proteinukalude phosphorylation vazhi niyantrikkaam.
phosphorylationte samvidaanangalum pravartthanangalum.
amino aasidukalude side cheyinil charjju cheythathum hydrophilic group phosphorylation avatharippikkunnu, ithu aduthulla amino aasidukalumayulla edapedalukalil maattam varuthunnathiloode oru proteente ghadanaye mattiyekkaam. pii53 polulla chila proteinukalil onniladhikam phosphorylation sittukal adangiyirikkunnu, ithu sankeernavum multy-level niyanthranavum sugamamakkunnu. proteinukal eluppathil phosphorilettu cheyyaanum defosphorilate cheyyaanum kazhiyunnathinaal, baahya signalukalodum paaristhithika saahacharyangalodum prathikarikkunnathinulla koshangalkkulla oru vazhakkamulla samvidaanamaanu itharathilulla parishkkaranam.
kainaasukal phosphorilettu proteinukalum phosphettekal defosphorilate proteinukalum. phosphorilation, defosphorilation ennivayiloode niravadhi ensaimukalum resepterukalum "oonaakkukayo" allengil "oof cheiyukayo cheiyunnu. reversible phosphorylation pala ensaimukalileyum resepterukalileyum ghadanayil oru anuroopa maattathinu kaaranamaakunnu, ithu avaa sajeevamo nirjjeevamo akkunnu. eucariotic proteinukalile serin, thrionin, tyrosine, histidin avashishtangalil phosphorylation saadhaaranayaayi sambhavikkunnu. eucariotic proteinukalude histidin phosphorilation tyrosine phosphorilationekkaal valare saadhaaranamaanennu thonnunnu. procariotic proteinukalil serin, thrionin, tyrosine, histidin allengil arjinin allengil lysine avashishtangalil phosphorylation sambhavikkunnu. amino assid avashishtangalude noonn-pollar aarr groupilekku oru phoosphett (pioo43-) thanmatra cherkkunnath oru proteente hydrophobic bhaagathe oru thanmaathrayude dhruvavum angeyattam hydrophilic bhagamaakki maattaan kazhiyum. eee reethiyil protein dynamics proteinile mattu hydrophobic, hydrophilic avashishtangalumayi deerghadoora alostariyiloode proteente ghadanayil oru anuroopa maattam varuthaan kazhiyum.
phosphorylation vahikkunna niyanthranaparamaaya punk pii53 tumour suppressor protein aanu. pii53 protein valareyadhikam niyanthrikkappedunnu, koodaathe 18-ladhikam vyathyastha phosphorylation sittukal adangiyirikkunnu. pii53 sajeevamaakkunnath sell saikkil arasttinu kaaranamakum, ithu chila saahacharyangalil vipareethamaakkaam, allengil apoptotic sell maranathilekku nayichekkaam. saadhaarana aarogyamulla vyakthikalil koshathinu kedupaadukal sambhavikkukayo shareeraghadanaye thadassappeduthukayo cheiyunna saahacharyangalil maathrame eee pravartthanam sambhavikkoo.
nirjjeevamaakkunna signalil, protein veendum defosphorylate cheyyappedukayum pravartthanam nirthukayum cheiyunnu. ithu pala tharatthilulla signal transduction samvidaanamaanu, udaaharanathinu rettinayude laitt sensitiivu cellukalil incoming prakasham prosess cheiyunna reethi.
phosphorylationte niyanthranaparamaaya punk ivayaanu
signalling netvarkkukal.
sankeernamaaya signalling paatha phosphorylation sambhavangal vyakthamaakkunnath budhimuttaayirikkum. sellular signalling pathakalil, protein eiii phosphorylates protein bii, bii phosphorylates sii. ennirunnaalum, mattoru signalling pathayil, protein dii phosphorylates eiii, allengil phosphorylates protein sii. proteomicsinte oru upashaakhayaaya phosphoproteomics polulla aagola sameepanagal, maas spectrometry adisthaanamaakkiyulla proteomicsumaayi samyojippichu phosphoproteomicsin chalanathmakamaaya mattangal thirichariyunnathinum alakkunnathinum upayogichittundu. sankeernamaaya phosphorylation shringalakalude chittayaya vishakalanathin eee saankethikavidyakal kooduthal praadhaanyamarhikkunnu. epidermal valarchaa gadakathodukoodiya uthejanathinu sesham 6000-ladhikam saittukalude phosphorylation nilayile chalanathmaka mattangal thirichariyaan avaa vijayakaramaayi upayogichu. phosphorylation shringhala manasilakkunnathinulla mattoru sameepanam, onniladhikam phosphorylating proteinukalum avayude lakshyangalum thammilulla janithaka edapedalukal alakkuka ennathaanu. ithu aashayavinimayangalude rasakaramaaya aavarthichulla paattenukal velippeduthunnu-network motifukal. phosphorylation nettvarkkukale maathrkayaakkunnathinum vyathyastha aswasthathakalkku keezhil avayude prathikaranangal pravachikkunnathinum computational reethikal vikasippicheduthittundu.
histonukalude phosphorylation.
kromaattin ennariyappedunna prathyeka samuchayangalil histoon proteinukal upayogichaanu eucariotic dna krameekarichirikkunnathu. kromaattin ghadana eucariotic dnaude packaging, oorganaiseshan, vitharanam enniva pravarthippikkukayum sugamamakkukayum cheiyunnu. ennirunnaalum, chila ensaimukaludeyum proteinukaludeyum labhyatha niyanthrikkunnathiloode transcription, replication, dna repire thudangiya niravadhi adisthaana jaiva prakriyakalil ithu prathikoola swaadheenam cheluthunnu. histoon phosphorilation polulla histonukalude vivarthanaananthara parishkkaranam protein dna allengil protein protein edapedalukal enniva maattunnathiloode kromaattin ghadanayil maattam varuthunnuvennu theliyikkappettittund. histoon poost-translation parishkkaranangal kromaattin ghadanaye parishkarikkunnu. dna kedupadukalkkulla sellular prathikaranangalil, phosphorylated histoon echu 2 eiii dna pottuna sthalathinu chuttumulla valia kromaattin domainukale verthirikkumbozhaanu ettavum saadhaaranayaayi bandhapetta histoon phosphorilation sambhavikkunnath. histonukalude parishkkaranangal rna polymerase II directed transcriptione nerittu baadhikkunnundo ennu gaveshakar parishodhichu. transcriptionil avayude phalangal parishodhikkunnathinaayi histonukale parishkkarikkunna proteinukal gaveshakar thiranjedukkunnu, koodaathe stress-induced kinace, emsk 1, rna sinthasisine thadayunnuvennu kandethi. kromaattinilillaatha dna templettukal emsk 1-nte phalangale prathirodhikkunnathinaal, msc 1-ll illaatha dna templettukal chromatinilaayirikkumbol emsk 1-nte transcription thadayunnathu ettavum sensitiivu aayirunnu. serin 1-ll emsk 1 phosphorylated histoon echu 2 eiii, serin 1-lake alanine parivartthanam cheiyunnathu emsk 1-nte transcription thadayunnuvennu kaanichu. athinaal phalangal soochippikkunnathu histonukalude asattileshan oru kinace vazhi emsk 1 aayi inhibittari phosphorilation adichamarthunnathiloode transcription uthejippikkaan kazhiyumennu.
kainaasukal.
oru proteinil, niravadhi amino aasidukalil phosphorylation sambhavikkam. serinile phosphorylation ettavum saadhaaranamaanennu karuthappedunnu, thudarnnu thrionin. tyrosine phosphorylation thaarathamyena apoorvamaanengilum pala protein phosphorylation signalling paathakaludeyum (udha.jii. mikka yookkaariyottukalilum tyrosine kainas-linked resepterukalil). serin, thrionin, tyrosine thudangiya amino aasidukalile phosphorylation oru phosphoprotein roopeekaranathinu kaaranamaakunnu, phosphoproteininte phoosphett group oru serr, threy, allengil tyre side cheyin ennivayude-ooo grouppumaayi oru esterification prathikaranatthil prathikarikkunnu. ennirunnaalum, tyrosine phosphorylated proteinukal aantibodikal upayogichu shudheekarikkaan thaarathamyena eluppamaayathinaal, tyrosine phosphorilation sittukal thaarathamyena nannayi manassilaakkappedunnu. rund ghadaka signalinginte bhaagamaayi prokaariyottukalilum chila saahacharyangalil chila signal transduction pathakalil yookkaariyottukalilum histidin, aspaarttett phosphorylation enniva sambhavikkunnu. staanderd biochemical, maas spectrometric sameepanagal upayogichu phosphorylated histidin vishakalanam cheiyunnathu serr, thru allengil tyrenekkaal valare velluvili niranjathaanu. prokaariyottukalil, aarkkiyayilum chila thaazhnna yookkaariyottukalil histidin naitrajan oru nucleophylayi pravartthikkukayum oru phoosphett grouppumaayi bandhippikkukayum cheiyunnu. histidin phosphorilettu cheythukazhinjaal, prathikarana regulatorinte niyanthrana domaine phoosphett aspaarttettilekk kaimaattam cheiyunnathinu uthejippikkunnu.
risapttar tyrosine kainaasukal.
tyrosine phosphorilation thaarathamyena kuranja samriddhiyil kaanappedunnundengilum, aantibodikal upayogichu phosphotyrosine shudheekarikkunnathu eluppamaakkunnathinaal ithu nannayi padikkappedunnu. hormonukal, valarchaa gadakangal, cytokainukal thudangiya extra sellular signalukalude transductionil earppettirikkunna sell uparithala resepterukalude oru pradhana kudumbamaanu risapttar tyrosine kainaasukal. oru ligand oru monomeric risapttar tyrosine kinesumaayi bandhippikkunnath rund monomerukal thammilulla edapedalukale sthirappeduthukayum oru diamer roopappeduthukayum cheiyunnu, athinusesham rund boundu resepterukal phosphorilettu tyrosine avashishtangal transil avasheshikkunnu. phosphorylation resepterinte sajeevamakkalum ensaimatik pravarthanatthiloodeyum adapter proteinukalumaayulla edapedalukaliloodeyum oru signalling paatha sajeevamaakkunnu. charmmam, shwaasakosham, hridayam, masthishkam ennivayulppede onniladhikam avayava samvidaanangalude vikasanathinu risapttar tyrosine kinace enna epidermal groth factor risapttar (iii. jii. eph. aarr) vazhi signalling nirnaayakamaan. pala manushya arbudangalilum iii. jii. eph. aarr. paathayiloode amithamaya signalling kaanapedunnu.
saiklin-ashrita kainaasukal.
eucariotic koshachakrathiloode purogathi niyanthrikkunna serin-thrionin kainesukalaanu saiklin-dependent kainesukal (sii. dii. keey. ezz). oru regulatory saiklin bandhikkumbol maathrame sii. dii. kall kaattalittikkaayi sajeevamaakoo. mrugakoshangalil kuranjathu ombathu vyathyastha sii. dii. kall adangiyirikkunnu, avaa ganyamaaya prathyekathayode vividha cyclinukalumaayi bandhippikkunnu. jii1-ll koshachakram thadayunnathino allengil paaristhithika signalukalo dna kedupaadukalo undaakunnathino sidike inhibittarukal (sii. keey. aii. ezz) saiklin-sidike complexile kinace pravartthanatthe thadayunnu. vividha sii. dii. keyude pravartthanam jii1/ezz ghatta parivartthanam polulla maittosisile pradhana sambhavangale niyanthrikkunna sell signalling paathakalum transcription gadakangalum sajeevamaakkunnu. munkaala saiklin-sidike complexukal thudarnnulla saiklin-sidike complexukal sajeevamakkunnathinulla signal nalkunnu.
sittukal.
oru prathyeka koshatthil aayirakkanakkin vyathyastha phosphorylation sittukal undu
oru nischitha proteinile eathenkilum saittinte phosphorylation aaa proteente pravartthanatheyo praadeshikavalkkaranatheyo maattaan kazhiyumennathinaal, oru koshatthinte "avastha" manasilakkaan athinte proteinukalude phosphorylation avastha ariyendathundu. udaaharanathinu, protein aaktile amino assid serin-473 ("s473") phosphorylated aanenkil, aakt pothuve oru kinace aayi pravarthanakshamamaanu. illengil, ithu oru nishkriya kinace aanu.
proteinukalkkum avayude gathaagathathinum pravarthanangalkkum phosphorylation sittukal nirnaayakamaan. reversible phosphorylationiloode proteinukalude kovalant parishkkaranamaan avaa. negatteevu phosphorylated saitt sellular membraniloode avayude praveshanakshamatha anuvadikkaathathinaal ithu proteinukale oru koshatthinullil akathu nilkkaan prapthamaakkunnu. protein defosphorylation pyrophosphateukal purathuvidunnathiloode phosphettukal niraykkaan koshatthe anuvadikkunnu, ithu koshatthile eiii. tii. pii upayogam laabhikkunnu. phosphorylating ensaiminte oru udaaharanam "iii" yill kaanapedunnu. koolii bacteria. athinte membranile periplasmic mekhalayil alkaline phosphatase undu. ettavum puram stharam phosphorylated thanmaathrakalilekku praveshikkaamenkilum valia negatteevu chaarjukal kaaranam aantharika cytoplasmic stharam abhedyamaanu. eee reethiyil, "iii. koolii bacteria proteinukalum pyrophosphateukalum koshatthinullil aavashyamaayi varunnathuvare athinte periplasmic membranil sambharikkunnu.
phosphoproteomic identificationile sameepakaala purogathi proteinukalile ennamatta phosphorylation saittukalude kandethalukalil kalaashichu. proteinukalude ariyappedunna phosphorylation sittukal krameekarichirikkunna axus cheyyaavunna daattaykk ithinu oru samyojitha maadyamam aavasyamaanu. echu" ennathil ariyappedunna phosphorylation sittukal adangiya dbpfinte oru curated daattaabes srishtichu. sapiens, "emm. musculus, "aarr. norvegicus, "dii. melanogaster, "sii. elegans, "ezz. pombe "umm" s "umm. serivisiye ". 40, 432 proteinukalude 29,4370 noonn-redendant phosphorylation saittukalaan nilavil daattaabesil ullathu. proteinukalile phosphorylation pravachanatthinte mattu upakaranagalil yookkaariyottukalkkulla netphos, baakteeriyakalkulla netfosback, vairasukalkkulla viralfose enniva ulppedunnu.
serin/thrionin.
serin avashishtangalkk vaividhyamund, oro avashishtathinteyum phosphorylation vyathyastha upapachayam prathyaaghaathangalilekku nayichekkaam. 
serin, thrionin avashishtangalude phosphorylation serin, thrionin avashishtangalude "ooo"-jii. ell. sii. enn. eiii. sii parishkkaranatthode crosstack cheiyunnathaayi ariyappedunnu.
tyrosine.
tyrosine phosphorylation vegathil prathipravartthikkukayum prathikaranam vipareethamaakkukayum cheyyaam. signal transduction-sell valarcha, deferentiation, migration, metaboolik homeostasis ennivayile pradhana niyanthrana samvidaanangalilonnaaya tyrosine phosphorilation paripaalikkunna sellular prakriyakalaanu. protein tyrosine kainesukaludeyum protein-tyrosine phosphatasinteyum pravartthanam eathoru proteinileyum phosphotyrosinte alavu santhulithamaakkunnu. protein tyrosine kainasinteyum protein tyrosine phosphatasinteyum prathyeka shringalakalude takaraar ponnatthadi, insulin prathirodham, type 2 diabetis melittas thudangiya onniladhikam manushya rogangalumaayi bandhappettirikkunnu. tyrosinte phosphorylation yookkaariyottukalil mathramalla sambhavikkunnath, marichu prokkariyottukalil kaanapedunna bacteria enangalil ithu kaanappedunnathayi kandethiyittundu. tyrosinte phosphorylation eukkaariyottukalile pravarthanatthinu samanamaaya baakteeriyayile sellular niyanthranam nilanirthunnu.
arjinain.
pala gram positteev bakteeriyakalileyum arjinin phosphorylation oru clp protees vazhi proteinukal kshayichupokunnathine adayaalappeduthunnu.
manushyakoshangalile addehathinte, asp, sis, glu, aarg, lies ennivayil noonn-canonical phosphorylation.
clair iii aiyezhs labil ninnulla sameepakaala padanangal helah sell sathil phosphorylated histidin (1,3 sthaanangal), aspaarttett, sisttin, glutamate, arjinin, lysine enniva adangiyirikkunna roopangal ulppede onniladhikam noonn-canonical amino aasidukalil vyapakamaaya manushya protein phosphorilation sthireekarikkunnu. eee phosphorylated avashishtangalude raasa, taapa sheshikal kaaranam, taapa sthirathayulla 'classical' serr, thru, tyre phosphorilation ennivaykkoppam samrakshanathinu prathyeka nadapadikramangalum verthirikkal saankethikavidyakalum aavasyamaanu.
kandethalum swabhaavasavisheshathayum.
oru prathyeka sthalathu oru protein phosphorylated aano ennu kandethaan sakthamaaya upakaranamaayi aantibodikal upayogikkaam. proteinile phosphorylation-preritha roopeekarana mattangal aantibodikal bandhippikkukayum kandethukayum cheiyunnu. atharam aantibodikale phospho-nirddishta aantibodikal ennu vilikkunnu; atharam noorukanakkinu aantibodikal ippol labhyamaan. adisthaana gaveshanathinum klinikkal roganirnayathinum avaa nirnaayaka reactorukalaayi maarukayaan.
poost translation modification (pii. tii. emm) isophomukal 2dii jellukalil eluppathil kandethanakum. theerchayaayum, serinukal, threonainukal allengil tyrosinukalile neutral hydroxyl grouppukale phosphorylation maattisthaapikkunnu, negatteevu charjju cheytha phosphettukal pii. keey. kall 1.2,6,5 ennivaykku aduthaanu. athinaal, piechu 5.5 nuu thaazhe, phosphettukal orotta negatteevu charge cherkkunnu; piechu 6.5 nuu sameepam, avaa 1.5 negatteevu chaarjukal cherkkunnu; piechu 7.5 nuu mukalil, avaa 2 negatteevu chaarjukal cherkkunnu. 2dii jelukalile karayude theevrathayil ninnu oro isophominteyum aapekshika alavu eluppathilum vegathilum nirnnayikkaan kazhiyum.
chila prathyeka sandarbhangalil, proteente electrophoretic chalanatthile oru mattamaayi phosphorylation kandethunnathu lalithamaaya 1-dimensional ezz. dii. ezz-peju jellukalil saadhyamaan, udaaharanathinu covax mattullavarum chernnu oru transcriptional koaktivettarinu ithu vivarikkunnu. sakthamaaya phosphorylationumaayi bandhapetta roopeekarana mattangal (dittarjant adangiya laayanikalil nilanilkkunnava) eee prathibhaasathinu adivarayidunnathaayi karuthappedunnu. atharam mobility shift vivarichittulla mikka phosphorylation saittukalum ezz. pii, tii. pii saittukalude vibhaagathil pedunnu (athaayath.iii. oru prolin avashishtam phosphorylated serin allengil thrionin avashishtathe pinthudarunnu).
aduthide protein phosphorylationte sthalangal nirnnayikkaan valia thothilulla maas spectrometry vishakalanangal upayogichittundu. kazhinja 4 varshathinide, dussen kanakkinu padanangal prasidheekarichu, oronnum aayirakkanakkin saittukale thiricharinju, avayil palathum munbu vivarikkappedaathavayirnu. phosphorylation cherkkunnath proteininteyum phosphorylated avashishtangaludeyum pindatthil vardhanavinu kaaranamakunnathinaal echsidy allengil eiii. tii. dii fragmentation upayogichu atharam vishakalanangalkk maas spectrometry anuyojyamaanu. eee padanangalkku noothanavum valare krithyathayullathumaaya maas spectrometerukal aavasyamaanu, ithu saankethikavidyaye uyarnna nilavaaramulla maas spectrometerukallu laabukalilekku parimithappedutthunnu. ennirunnaalum, maas spectrometry vazhi phosphorylated pepttaidukalude vishakalanam ippozhum "saadhaarana", parishkkarikkappedaathu pepttaidukaleppole nereyalla. electron-transfer uyarnna oorjja koottiyidi vighadanavum samyojippichu aduthide ethidy vikasippicheduthittundu. saadhaarana vighadana reethikalumaayi thaarathamyappeduthumbol, ethsidy skeem avyakthamaaya phosphosit praadeshikavalkkaranathinu kooduthal vivaradaayakamaaya ems/ems spectra nalkunnu.
phosphorylation saittukalude vishadamaaya swabhaavasavisheshatha valare budhimuttaanu, maas spectrometry vazhi protein phosphorylationte alavu kanakkakkaan isotopic aantharika staanderd sameepanagal aavasyamaanu. vividatharam deferential isotope labeling saankethikavidyakal upayogichu oru aapekshika alavu nedaanaakum. fluorescence immunoasse, microskeyil thermophoresis, frettu, tii. aarr. eph, fluorescence polaraiseshan, fluorescence-shamippikkal, mobility shift, beed adhishtitha kandethal, sell adhishtitha formaattukal ennivayulppede niravadhi alavilulla protein phosphorilation reethikalum undu.
parinamam.
ellah mrugangal, sasyangal, fungus, bacteria, archaea ennivayulppede ellah jeevajaalangalilum protein phosphorylation saadhaaranamaanu. protein phosphorylation samvidaanangalude uthbhavam poorvvikaraanu, avaa vividha speesheesukalkkidayil valareyadhikam verpirinjirikkunnu. yookkaariyottukalil, ellah proteinukaludeyum <aii. dii. 1>-num idayil pathinaayirakkanakkin allengil lakshakkanakkin vyathyastha phosphorylation sittukalulla phosphorylated aayirikkaamenn kanakkaakkappedunnu. chila phosphorylation sittukal vyavasthaapithamaaya "oof" svichukalaayi parinamichathaayi thonnunnu, ithu procariotic metaboolik ensime isositrettu dehydrogenase polulla oru ensaiminte sajeeva saittine thadayunnu. ennirunnaalum, sajeevamakaan phosphorylated aayirikkenda proteinukalude kaaryatthil, phosphorylated allatha poorvvikaril ninnu avaa engane uyarnnuvannuvennu vyakthamalla. serin phosphocytukalude oru upavibhaagathin pakaram palappozhum vividha speesheesukalkkidayil aspaarttett, glutamate thudangiya acidity avashishtangal undennu theliyikkappettittund. eee ionic avashishtangalkk lysine, arjinin thudangiya catianic avashishtangalumayi samvadichu uppu paalangal, oru proteente ghadanaye mattunna sthirathayulla noonn-kovalant edapedalukal enniva undakkaan kazhiyum. eee phosphocytukal palappozhum uppu paalangalil pankedukkunnu, chila phosphorylation sittukal uppu palangalkkulla vyavasthaapitha svichukalaayi parinamichuvennu soochippikkunnu, ithu eee proteinukale oru prathyeka signalinodulla prathikaranatthil maathram sajeevamaaya oru roopeekaranam sweekarikkaan anuvadikkunnu.
ariyappedunna 600 eucariotic protein kainesukalundu, ithu avaye ettavum valia jeane kudumbangalilonnayi maattunnu. mikka phosphorylation nadathunnathu oru samrakshitha kinace domaine pankidunna protein kainesukalude orotta suuppar faamiliyaan. saiklin-dependent kainaasukale (sii. dii. keey. ezz) aasrayikkunna koshachakra purogathi polulla koshangalude athijeevanathinte kendra pathakalil protein phosphorylation valareyadhikam samrakshikkappedunnu, ennaal vyakthigatha phosphorylation sittukal palappozhum vazhakkamullavayaan. sii. dii. keey phosphorylationte lakshyangalil palappozhum kramarahithamaya bhaagangalil phosphocytukal undu, avaa adutha speesheesukalil polum samaanamallatha sthalangalil kaanapedunnu. neremarichu, gadanaaparamaayi nirvachikkapetta pradeshangalile sii. dii. keey phosphorylationte lakshyangal kooduthal samrakshikkappedunnu. ellah yookkaariyottukalileyum koshavalarchaykkum atijeevanathinum sii. dii. keey pravartthanam nirnaayakamaanenkilum, valare kurachu phosphocytukal maathrame avayude krithyamaaya sthaanangalude sakthamaaya samrakshanam kaanikkunnulloo. protein ghadanaye alosterikkaayi niyanthrikkunna fosfettukalkku positioning valare pradhaanamaan, ennaal regulatory proteinukale recruit cheiyunnathinu phosphopeptide-binding domainukalumaayi edapazhakunna fosfettukalkku ithu kooduthal vazhakkamullathaan.
eukkaariyottukalum prokaariyottukalum thammilulla thaarathamyangal.
proteinukalude vivarthanaananthara maattam maattaavunna oru parivarthanamaanu protein phosphorylation. yookkaariyottukalil, protein phosphorylation sell signalling, jeane expression, deferentiation ennivayil pravartthikkunnu. koshachakratthil dna replicationilum sammarda preritha replication blokkukale neridunna samvidaanangalilum ithu ulppedunnu. yookkaariyottukalumaayi thaarathamyappeduthumbol, prokaariyottukal signal traansdakshanaayi hanks-type kainesukalum phosphataseukalum upayogikkunnu. baakteeriyakalile proteinukalude phosphorylation dna repire allengil replication polulla prakriyakale niyantrikkaan kazhiyumo illayo ennathu ippozhum vyakthamalla.
prokaariyottukalude protein phosphorylationumaayi thaarathamyappeduthumbol, yookkaariyottukalil yeest muthal manushyakoshangal vareyulla protein phosphorylationecurichlu padanangal valare vipulamaanu. sell signalinginaayi serin, thrionin, tyrosine ennivayude side cheyinukalile hydroxyl grouppinte phosphorylatione yookkariyottukal aashrayikkunnuvenn ariyappedunnu. eucariotic koshangalile pradhana niyanthrana poost-translation parishkkaranangalaaniva, ennaal prokaariyottukalude protein phosphorylation valare kuravaanu. serin, thrionin, tyrosine enniva yookkaariyottukalil phosphorylated aanenkil, histidin, aspaarttett enniva prokaariyottukal, sasyangal, noonn-plaant yookkariyottukal ennivayil phosphorylated aanu. bakteeriyakalil, histidin phosphorilation sambhavikkunnath phosphoyenolpyruvettu-dependent phosphotranspherase sistangalilaanu (pts), avaa aantharikavalkkarana prakriyayilum panchasaarayude phosphorilation prakriyayilum ulppedunnu.
protein kinace upayogichulla protein phosphorylation aadyamaayi "iii" yill kaanichu. koolii, salmonella typhimurium enniva ennaal pinneedu mattu pala bacteria koshangalilum prakadamaayittundu. bacteria signalling transductionulla oru maathrkayaayi bakteeriyakal histidin, aspaarttett phosphorilation enniva upayogikkunnuvennu kandethi, ennaal kazhinja kurachu varshangalayi serin, thrionin, tyrosine phosphorilation ennivayum bakteeriyakalil undennu theliyikkunna thelivukal undu. bakteeriyakal avayude eucariotic thulyamaaya kainesukalum phosphataseukalum vahikkunnuvennu theliyikkapettu, ennaal avaa yookkaariyottukalil kaanaatha savisheshamaaya kainesukalum phosphataseukalum vikasippicheduthittundu.
pathology.
asaadhaaranamaaya protein phosphorylation niravadhi rogangalil ulppettittund, prathyekichu cancer, mathramalla alsheimer rogam, paarkkinsans rogam, mattu degenerative disordezhs ennivayum.
neuronukal ulppedeyulla koshangalile microtubilukale sthirappeduthaan sahayikkunna microtubilumaayi bandhapetta proteinukalude (maappukal) oru koottatthil taavu protein ulppedunnu. tow proteininte bandhavum sthiratha kaivarikkunnathumaya pravartthanam athinte phosphorylated avasthaye aasrayichirikkunnu. alshimezhs rogathil, tow protein gadanayile thettaaya madakkukalum asaadhaaranamaaya roopeekarana maattangalum kaaranam, ithu microtubilukalumaayi bandhippikkunnathil falapradamallaathathaakkukayum athinaal neural prakriyakalil neural cytoskelital ghadana krameekarikkaan kazhiyaathe varikayum cheiyunnu; vaasthavathil asaadhaaranamaaya tow microtuble oorganaiseshane thadayukayum thadassappeduthukayum cheiyunnu, koodaathe microtubilukalil ninnu saadhaarana touye cytosolic ghattathilekku verthirikkunnu. thettaaya madakkangal neuronukalkkullile fibrillary taamgilukalilekkulla asaadhaaranamaaya othucheralilekku nayikkunnu, ithu alsheimer rogathinte mukhamudrayaanu. tow protein pravartthikkaan mathiyaya alavil phosphorilettu cheyyendathundu, ennaal tow proteente hyperphosphorylation athinte bandhappeduthaanulla kazhivillaaymaye badhikkunna pradhana swaadheenangalilonnaayi kanakkaakkappedunnu. phosphatases pipi1, pipi2eiii, pipi2bii, pipi2sii defosphorilate tow protein "inn vitro" ennivayil alsheimer rogikalil thalachorinte bhaagangalil avayude pravartthanangal kurayunnathaayi kandethiyittundu. prayamaaya rogikalallaatha oru vyakthiye apekshichu oru alsheimer rogiyil tow phosphoprotein moonnu muthal naalu madangu vare hyperphosphorylated aanu. alshimer disease tow microtubilukalil ninnu mapp 1, mapp 2 (mattu rund pradhana anubandha proteinukal) enniva neekkam cheiyunnathaayi thonnunnu, koodaathe defosphorylation nadathumbol eee doshakaramaaya prabhavam vipareethamaakunnu, ithu hyperphosphorylation aanu amgavaikalya pravartthanatthinte eaka kaaranam ennu theliyikkunnu.
paarkkinsans rogam.
paarkkinsans rogavumaayi bandhapetta oru proteinaan α-synculine. manushyaril eee protein "snca" jeane encode cheythirikkunnu.neuro traansmittarukal vahikkunna synaptic vesikkilukalude recyclingil α-synculine ulppedunnu, ithu swaabhaavikamaayum oru thuranna roopathil sambhavikkunnu. paarkkinsans rogamulla rogikalil α-synculinte uyarnna alavu kaanapedunnu, koodaathe rogiyil adangiyirikkunna α-synculine proteente alavum rogathinte kaadinyavum thammil oru nalla parasparabandhamundennu thonnunnu.
α-synculine proteinile amino assid serr129-nte phosphorylation rogathinte theevrathayil aazhathilulla swaadheenam cheluthunnu. paarkkinsans rogikalile motham α-synculine saandrathayum (phosphorylated allatha) lakshanangalude theevrathayum thammil paraspara bandhamundennu thonnunnu. aarogyamulla rogikalkku paarkkinsans rogamulla rogikale apekshichu uyarnna alavil phosphorylated α-synculine undennu thonnunnu. koodaathe, oru rogikkullil phosphorylated α-sinuklin, unfosphorylated α-sinuklin ennivayude saandrathayude anupaathatthile maattangalude alavu rogathinte purogathiyude oru marker aakam. phosphorylated serin 129-ll α-sinuclean lakshyamidunna aantibodikal sinuklinoppathi rogangalude tanmatra vashangal padikkaan vyaapakamaayi upayogikkunnu. 
serr129-nte phosphorylation protein samaaharikkunnathumaayum naadeevyavasthaykku kooduthal kedupaadukal varuthunnathumayum bandhappettirikkunnu. koodaathe, oru pree synaptic scarfold protein septt 4 aparyapthamaaya alavil undengil phosphorylated α-sinuklininte samaharanam vardhippikkaan kazhiyum. septt4 proteinumaayulla α-synculinte nerittulla edapedal serr129-nte phosphorylatione thadayunnu ennathu sradhikkendathaanu. ennirunnaalum, serr129-nte phosphorylation amithamaya expression saahacharyangalil sinuklin aggregation illaathe nireekshikkaan kazhiyumennu shradhikkuka.