RPS6KB1

Ribosomna protein S6 kinaza beta-1 (S6K1), znana i kao p70S6 kinaza (p70S6K, p70-S6K), je enzim (preciznije protein-kinaza) koji je kod ljudi kodiran genom RPS6KB1.^[5][6] To je serin / treonin kinaza koja djeluje nizvodno od PIP3 i fosfoinozitid-ovisne kinaze-1 u PI3 kinaznom putu.^[7] Kao što i samo ime govori, njegov cilj supstrat je ribosomski protein S6.^[8] Sintezu proteina na ribosomu nducira fosforilacija S6.

RPS6KB1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 3A60, 3A61, 3A62, 3WE4, 3WF5, 3WF6, 3WF7, 3WF8, 3WF9, 4L3J, 4L3L, 4L42, 4L43, 4L44, 4L45, 4L46, 4RLO, 4RLP
Identifikatori
Aliasi	RPS6KB1
Vanjski ID-jevi	OMIM: 608938 MGI: 1270849 HomoloGene: 81703 GeneCards: RPS6KB1
Lokacija gena (čovjek) Hrom. Hromosom 17 (čovjek)[1] Bend 17q23.1 Početak 59,893,046 bp[1] Kraj 59,950,574 bp[1]
Lokacija gena (miš) Hrom. Hromosom 11 (miš)[2] Bend 11|11 C Početak 86,498,871 bp[2] Kraj 86,544,805 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • aktivnost sa transferazom • protein kinase activity • nucleotide binding • peptide binding • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje identičnih proteina • protein serine/threonine/tyrosine kinase activity • ATP binding • kinase activity • protein serine/threonine kinase activity • ribosomal protein S6 kinase activity • PDZ domain binding • protein phosphatase 2A binding Ćelijska komponenta • citoplazma • citosol • membrana • sinapsa • nukleoplazma • cell surface • mitochondrial outer membrane • međućelijske veze • mitohondrija • perinuklearno područje citoplazme • neuron projection • jedro Biološki proces • germ cell development • response to amino acid • response to glucagon • GO:1904578 response to organic cyclic compound • protein kinase B signaling • response to nutrient • Fosforilacija • regulation of glucose import • response to testosterone • negative regulation of extrinsic apoptotic signaling pathway • cellular response to growth factor stimulus • skeletal muscle contraction • response to mechanical stimulus • GO:0010260 Starenje • response to leucine • GO:1904579 cellular response to organic cyclic compound • positive regulation of mitotic cell cycle • negative regulation of apoptotic process • response to heat • response to glucocorticoid • response to glucose • response to peptide hormone • behavioral fear response • positive regulation of translation • response to organic substance • positive regulation of smooth muscle cell migration • response to tumor necrosis factor • response to insulin • response to lipopolysaccharide • GO:1903105 negative regulation of insulin receptor signaling pathway • cellular response to hormone stimulus • Dugoročno pamćenje • response to wounding • response to organonitrogen compound • response to electrical stimulus involved in regulation of muscle adaptation • skeletal muscle atrophy • ćelijski ciklus • response to ethanol • positive regulation of translational initiation • Ćelijska migracija • response to toxic substance • positive regulation of skeletal muscle tissue growth • regulation of translation • phosphatidylinositol-mediated signaling • GO:0072468 Transdukcija signala • positive regulation of smooth muscle cell proliferation • GO:0097285 apoptoza • protein phosphorylation • cellular response to dexamethasone stimulus • cellular response to insulin stimulus • G1/S transition of mitotic cell cycle • GO:0035404 peptidyl-serine phosphorylation • TOR signaling • cellular response to interferon-gamma • long-chain fatty acid import into cell • GO:0007243 intracellular signal transduction • response to nutrient levels Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	6198	72508
Ensembl	ENSG00000108443	ENSMUSG00000020516
UniProt	P23443	Q8BSK8
RefSeq (mRNK)	NM_001272042 NM_001272043 NM_001272044 NM_001272060 NM_003161	NM_001114334 NM_028259 NM_001363162
RefSeq (bjelančevina)	NP_001258971 NP_001258972 NP_001258973 NP_001258989 NP_003152 NP_001356598 NP_001356599 NP_001356600 NP_001356601 NP_001356602 NP_001356603 NP_001356604 NP_001356605 NP_001356606 NP_001356607 NP_001356608	NP_001107806 NP_082535 NP_001350091
Lokacija (UCSC)	Chr 17: 59.89 – 59.95 Mb	Chr 11: 86.5 – 86.54 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Fosforilacija p70S6K na treoninu 389 korištena je kao obilježje aktivacije od mTOR i u korelaciji je s inhibicijom autofagija u različitim situacijama. Međutim, nekoliko nedavnih studija sugerira da aktivnost p70S6K ima pozitivniju ulogu u porastu autofagije.^[9][10]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 525 aminokiselina, a molekulska težina 59.140 Da.^[11].

10		20		30		40		50
MRRRRRRDGF		YPAPDFRDRE		AEDMAGVFDI		DLDQPEDAGS		EDELEEGGQL
NESMDHGGVG		PYELGMEHCE		KFEISETSVN		RGPEKIRPEC		FELLRVLGKG
GYGKVFQVRK		VTGANTGKIF		AMKVLKKAMI		VRNAKDTAHT		KAERNILEEV
KHPFIVDLIY		AFQTGGKLYL		ILEYLSGGEL		FMQLEREGIF		MEDTACFYLA
EISMALGHLH		QKGIIYRDLK		PENIMLNHQG		HVKLTDFGLC		KESIHDGTVT
HTFCGTIEYM		APEILMRSGH		NRAVDWWSLG		ALMYDMLTGA		PPFTGENRKK
TIDKILKCKL		NLPPYLTQEA		RDLLKKLLKR		NAASRLGAGP		GDAGEVQAHP
FFRHINWEEL		LARKVEPPFK		PLLQSEEDVS		QFDSKFTRQT		PVDSPDDSTL
SESANQVFLG		FTYVAPSVLE		SVKEKFSFEP		KIRSPRRFIG		SPRTPVSPVK
FSPGDFWGRG		ASASTANPQT		PVEYPMETSG		IEQMDVTMSG		EASAPLPIRQ
PNSGPYKKQA		FPMISKRPEH		LRMNL

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Funkcija

Ovaj gen kodira člana RSK porodice serin / treonin kinaza. Ova kinaza sadrži dva neidentična katalitska domena kinaze i fosforilira nekoliko ostataka ribosomskog proteina S6. Aktivnost kinaze ovog proteina dovodi do povećanja sinteze proteina i proliferacije ćelija. Pojačanje regije DNK koja kodira ovaj gen i prekomerna ekspresija ove kinaze uočene su u nekim ćelijskim linijama karcinoma dojke. Opisana su alternativna mjesta translacije i varijante prerađenih transkripata, ali nisu detaljno okarakterizirana.

mTOR

P70S6 kinaza je nizvodna meta signalizacije mTOR (cilj sisarskog rapamicina), posebno mTORC1, kompleksa koji sadrži mTOR, a karakterizira se uključivanjem Raptora, a ne Riktora (mTORC2). mTOR se može aktivirati putem mehanizma sličnog AND-vratima u lizosomu, integrirajući signale o faktorima rasta i bioraspoloživosti važnih molekula. Naprimjer, aminokiseline poput arginina i leucina mogu podstaknuti lizosomsko regrutiranje mTORC1. Kada se nađe u lizosomu, mTOR može aktivirati Rheb, malu GTPazu, koja se nalazi u lizosomu, u svom stanju vezanom za GTP. Aktivnost reb GTPaze stimulira (i samim tim smanjuje kapacitet za aktiviranje mTOR) uzvodnim TSC kompleksom, koji je inhibiran IGF signalizacijom. Stoga se AND ulaz sastoji od pravilne lokalizacije dovoljnom količinom aminokiselina i aktivacije faktorima rasta. Jednom kada je mTOR pravilno lokaliziran i aktiviran, može fosforilirati nizvodne ciljeve kao što su p70S6K, 4EBP i ULK1, koji su važni za regulaciju anaboličke/ kataboličke ravnoteže proteina. Fizička vježba aktivira sintezu proteina, fosforilacijom (aktivacijom) p70S6K na putu koji ovisi o mTOR, konkretno mTORC1. To je dokazano upotrebom inhibitora mTOR-a, rapamicina, za blokiranje povećanja mišićne mase, uprkos povećanom opterećenju (npr. vježbanjem). Pokazalo se da vježba povećava nivo IGF-1 u mišićima, indukujući tako signalni put IGF-1/PI3K/Akt/p70S6K, a samim tim povećanu sintezu proteina potrebnih za izgradnju mišića.

Klinički značaj

Inhibicija proteina S6K1, ili njegov nedostatak, usporava proizvodnju masnih ćelija, ometanjem i usporavanjem početne "faze posvećenosti" njihovom formiranju. Studija bi mogla imati implikacije na liječenje gojaznosti.^[12]

Amplifikacija regije DNK koja kodira ovaj gen i prekomerna ekspresija ove kinaze uočena je kod nekih karcinoma dojke u ćelijskim linijama.

Sljedeći put, za koji je P70 predložio njegovosudjelovanje, produžuje i rast mišića. P70 se fosforilira pasivnim istezanjem u mišićima. Ovo je možda jedna od mnogih proteinskih kinaza uključenih u izgradnju mišića.^[13]

U svom neaktivnom stanju, S6K1 je vezan za eIF3 i odvaja se nakon fosforilacije, pomoću mTOR/Raptor-a. Slobodni S6K1 tada može fosforilirati svoje brojne ciljeve, uključujući eIF4B.^[14]

Interakcije

Pokazano je da P70-S6 kinaza 1 komunicira sa:

• COASY,^[15]
• CSNK2B,^[16]
• EIF3B,^[17]
• KIAA1303,^{[18][19][20][21]}
• MTOR,^{[22][23][24][25][26][27][28][29][30][31][32][33]}
• POLDIP3,^[34]
• PPP2R2A,^[35][36]
• RBX1,^[37] i
• UBC.^[37]

Također pogledajte

• Ribosomna S6 kinaza
• RPS6KA1

Reference

1. GRCh38: Ensembl release 89: ENSG00000108443 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020516 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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6. "Entrez Gene: RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1".
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Vanjski linkovi

• P23443

Portal Biologija