AKT1

gene da espécie Homo sapiens

AKT1, do inglês V-akt murine thymoma viral oncogene homolog 1, é uma enzima que em humanos é codificada pelo gene AKT1.

AKT1
Estruturas disponíveis
PDBPesquisa Human UniProt: PDBe RCSB
Identificadores
Nomes alternativosAKT1
IDs externosOMIM: 164730 HomoloGene: 3785 GeneCards: AKT1
Doenças Geneticamente Relacionadas
cancro colorretal, síndrome de Proteus, cancro da mama, Síndrome de Cowden[1]
Wikidata
Ver/Editar Humano

A proteína quinase serina/treonina codificada pelo gene AKT1 está cataliticamente inactiva em fibroblastos privados de soro e em fibroblastos imortalizados. AKT1 e o ATK2 são activados por factores de crescimento derivados de plaquetas. A activação é rápida e específica, não sendo anulada por mutações no domínio de homologia a plecstrina da AKT1. Foi demonstrado que a activação ocorre através do fosfoinositol 3-quinase.

No sistema nervoso em desenvolvimento, o AKT é um mediador crítico da sobrevivência neuronal induzida por factores de crescimento. Os factores de crescimento podem suprimir a apoptose de uma maneira independente de transcrição, por activação da quinase serina/treonina AKT1, que depois fosforila e inactiva componentes da apoptose.

Múltiplos variantes de transcriptos, que sofreram splicing alternativo, foram encontrados para este gene.[3]

Ratos que não possuem AKT1 mostram uma redução em 25% da massa corporal, indicando que este gene é fundamental para que os sinais dos factores de crescimento sejam transmitidos, mais provavelmente através do receptor IGF1. Os ratos que não possuem AKT1 são também resistentes ao cancro: apresentam atrasos consideráveis no crescimento de tumores iniciados, por exemplo pelo oncogene NEU.

Interações editar

AKT1 mostrou interação com Phosphoinositide-dependent kinase-1,[4][5] Keratin 10,[6] Integrin-linked kinase,[4][5][7] TSC2,[8][9] GAB2,[10] TRIB3,[11] NPM1,[12] BRCA1,[13][14] BRAF,[15] C-Raf,[16] MAPK14,[17] MARK2,[18] MAP2K4,[19] MTCP1,[20][21] TCL1A,[20][21][22] Nerve Growth factor IB,[23] MAPKAPK2,[17] PRKCQ,[24] Androgen receptor,[25] Heat shock protein 90kDa alpha (cytosolic), member A1,[26][27][28] Plexin A1,[29] MAP3K11,[30] TSC1,[8][9] MAP3K8,[31] Mammalian target of rapamycin,[32][33][34] PKN2,[35] AKTIP,[36] YWHAZ,[37] CHUK[38][39] e CDKN1B.[40]

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Referências

  1. «Doenças geneticamente associadas a AKT1 ver/editar referências no wikidata» 
  2. «Human PubMed Reference:» 
  3. «Entrez Gene: AKT1 v-akt murine thymoma viral oncogene homolog 1» 
  4. a b Barry, Fiona A; Gibbins Jonathan M (Abril de 2002). «Protein kinase B is regulated in platelets by the collagen receptor glycoprotein VI». United States. J. Biol. Chem. 277 (15): 12874–8. ISSN 0021-9258. PMID 11825911. doi:10.1074/jbc.M200482200 
  5. a b Persad, S; Attwell S, Gray V, Mawji N, Deng J T, Leung D, Yan J, Sanghera J, Walsh M P, Dedhar S (Julho de 2001). «Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343». United States. J. Biol. Chem. 276 (29): 27462–9. ISSN 0021-9258. PMID 11313365. doi:10.1074/jbc.M102940200 
  6. Paramio, J M; Segrelles C, Ruiz S, Jorcano J L (Novembro de 2001). «Inhibition of protein kinase B (PKB) and PKCzeta mediates keratin K10-induced cell cycle arrest». United States. Mol. Cell. Biol. 21 (21): 7449–59. ISSN 0270-7306. PMC 99917 . PMID 11585925. doi:10.1128/MCB.21.21.7449-7459.2001 
  7. Delcommenne, M; Tan C, Gray V, Rue L, Woodgett J, Dedhar S (Setembro de 1998). «Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase». UNITED STATES. Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11211–6. ISSN 0027-8424. PMC 21621 . PMID 9736715. doi:10.1073/pnas.95.19.11211 
  8. a b Dan, Han C; Sun Mei, Yang Lin, Feldman Richard I, Sui Xue-Mei, Ou Chien Chen, Nellist Mark, Yeung Raymond S, Halley Dicky J J, Nicosia Santo V, Pledger Warren J, Cheng Jin Q (Setembro de 2002). «Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin». United States. J. Biol. Chem. 277 (38): 35364–70. ISSN 0021-9258. PMID 12167664. doi:10.1074/jbc.M205838200 
  9. a b Roux, Philippe P; Ballif Bryan A, Anjum Rana, Gygi Steven P, Blenis John (Setembro de 2004). «Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase». United States. Proc. Natl. Acad. Sci. U.S.A. 101 (37): 13489–94. ISSN 0027-8424. PMC 518784 . PMID 15342917. doi:10.1073/pnas.0405659101 
  10. Lynch, Danielle K; Daly Roger J (Janeiro de 2002). «PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2». England. EMBO J. 21 (1-2): 72–82. ISSN 0261-4189. PMC 125816 . PMID 11782427. doi:10.1093/emboj/21.1.72 
  11. Du, Keyong; Herzig Stephan, Kulkarni Rohit N, Montminy Marc (Junho de 2003). «TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver». United States. Science. 300 (5625): 1574–7. PMID 12791994. doi:10.1126/science.1079817 
  12. Lee, Sang Bae; Xuan Nguyen Truong L, Choi Joung Woo, Lee Kyung-Hoon, Cho Sung-Woo, Liu Zhixue, Ye Keqiang, Bae Sun Sik, Ahn Jee-Yin (Outubro de 2008). «Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival». United States. Proc. Natl. Acad. Sci. U.S.A. 105 (43): 16584–9. PMC 2569968 . PMID 18931307. doi:10.1073/pnas.0807668105 
  13. Altiok, S; Batt D, Altiok N, Papautsky A, Downward J, Roberts T M, Avraham H (Novembro de 1999). «Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells». UNITED STATES. J. Biol. Chem. 274 (45): 32274–8. ISSN 0021-9258. PMID 10542266. doi:10.1074/jbc.274.45.32274 
  14. Xiang, Tao; Ohashi Amiko, Huang Yuping, Pandita Tej K, Ludwig Thomas, Powell Simon N, Yang Qin (Dezembro de 2008). «Negative Regulation of AKT Activation by BRCA1». United States. Cancer Res. 68 (24): 10040–4. PMC 2605656 . PMID 19074868. doi:10.1158/0008-5472.CAN-08-3009 
  15. Guan, K L; Figueroa C, Brtva T R, Zhu T, Taylor J, Barber T D, Vojtek A B (Setembro de 2000). «Negative regulation of the serine/threonine kinase B-Raf by Akt». UNITED STATES. J. Biol. Chem. 275 (35): 27354–9. ISSN 0021-9258. PMID 10869359. doi:10.1074/jbc.M004371200 
  16. Zimmermann, S; Moelling K (Novembro de 1999). «Phosphorylation and regulation of Raf by Akt (protein kinase B)». UNITED STATES. Science. 286 (5445): 1741–4. ISSN 0036-8075. PMID 10576742. doi:10.1126/science.286.5445.1741 
  17. a b Rane, M J; Coxon P Y, Powell D W, Webster R, Klein J B, Pierce W, Ping P, McLeish K R (Fevereiro de 2001). «p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils». United States. J. Biol. Chem. 276 (5): 3517–23. ISSN 0021-9258. PMID 11042204. doi:10.1074/jbc.M005953200 
  18. Dickey, Chad A; Koren John, Zhang Yong-Jie, Xu Ya-Fei, Jinwal Umesh K, Birnbaum Morris J, Monks Bobby, Sun Mei, Cheng Jin Q, Patterson Cam, Bailey Rachel M, Dunmore Judith, Soresh Sareh, Leon Carlos, Morgan Dave, Petrucelli Leonard (Março de 2008). «Akt and CHIP coregulate tau degradation through coordinated interactions». United States. Proc. Natl. Acad. Sci. U.S.A. 105 (9): 3622–7. PMC 2265134 . PMID 18292230. doi:10.1073/pnas.0709180105 
  19. Park, Hee-Sae; Kim Mi-Sung, Huh Sung-Ho, Park Jihyun, Chung Jongkyeong, Kang Sang Sun, Choi Eui-Ju (Janeiro de 2002). «Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation». United States. J. Biol. Chem. 277 (4): 2573–8. ISSN 0021-9258. PMID 11707464. doi:10.1074/jbc.M110299200 
  20. a b Laine, Jarmo; Künstle Gerald, Obata Toshiyuki, Noguchi Masayuki (Fevereiro de 2002). «Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family». United States. J. Biol. Chem. 277 (5): 3743–51. ISSN 0021-9258. PMID 11707444. doi:10.1074/jbc.M107069200 
  21. a b Laine, J; Künstle G, Obata T, Sha M, Noguchi M (Agosto de 2000). «The protooncogene TCL1 is an Akt kinase coactivator». UNITED STATES. Mol. Cell. 6 (2): 395–407. ISSN 1097-2765. PMID 10983986. doi:10.1016/S1097-2765(00)00039-3 
  22. French, Samuel W; Shen Rhine R, Koh Patricia J, Malone Cindy S, Mallick Parag, Teitell Michael A (Maio de 2002). «A modeled hydrophobic domain on the TCL1 oncoprotein mediates association with AKT at the cytoplasmic membrane». United States. Biochemistry. 41 (20): 6376–82. ISSN 0006-2960. PMID 12009899. doi:10.1021/bi016068o 
  23. Pekarsky, Y; Hallas C, Palamarchuk A, Koval A, Bullrich F, Hirata Y, Bichi R, Letofsky J, Croce C M (Março de 2001). «Akt phosphorylates and regulates the orphan nuclear receptor Nur77». United States. Proc. Natl. Acad. Sci. U.S.A. 98 (7): 3690–4. ISSN 0027-8424. PMC 31113 . PMID 11274386. doi:10.1073/pnas.051003198 
  24. Bauer, B; Krumböck N, Fresser F, Hochholdinger F, Spitaler M, Simm A, Uberall F, Schraven B, Baier G (Agosto de 2001). «Complex formation and cooperation of protein kinase C theta and Akt1/protein kinase B alpha in the NF-kappa B transactivation cascade in Jurkat T cells». United States. J. Biol. Chem. 276 (34): 31627–34. ISSN 0021-9258. PMID 11410591. doi:10.1074/jbc.M103098200 
  25. Lin, H K; Yeh S, Kang H Y, Chang C (Junho de 2001). «Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor». United States. Proc. Natl. Acad. Sci. U.S.A. 98 (13): 7200–5. ISSN 0027-8424. PMC 34646 . PMID 11404460. doi:10.1073/pnas.121173298 
  26. Haendeler, Judith; Hoffmann Jörg, Rahman Sandy, Zeiher Andreas M, Dimmeler Stefanie (Fevereiro de 2003). «Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation». Netherlands. FEBS Lett. 536 (1-3): 180–6. ISSN 0014-5793. PMID 12586360. doi:10.1016/S0014-5793(03)00058-9 
  27. Kawauchi, Kiyotaka; Ihjima Kimiko, Yamada Osamu (Maio de 2005). «IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells». United States. J. Immunol. 174 (9): 5261–9. ISSN 0022-1767. PMID 15843522 
  28. Sato, S; Fujita N, Tsuruo T (Setembro de 2000). «Modulation of Akt kinase activity by binding to Hsp90». UNITED STATES. Proc. Natl. Acad. Sci. U.S.A. 97 (20): 10832–7. ISSN 0027-8424. PMC 27109 . PMID 10995457. doi:10.1073/pnas.170276797 
  29. Turner, Laura J; Nicholls Sarah, Hall Alan (Agosto de 2004). «The activity of the plexin-A1 receptor is regulated by Rac». United States. J. Biol. Chem. 279 (32): 33199–205. ISSN 0021-9258. PMID 15187088. doi:10.1074/jbc.M402943200 
  30. Barthwal, Manoj K; Sathyanarayana Pradeep, Kundu Chanakya N, Rana Basabi, Pradeep Anamika, Sharma Chandan, Woodgett James R, Rana Ajay (Fevereiro de 2003). «Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival». United States. J. Biol. Chem. 278 (6): 3897–902. ISSN 0021-9258. PMID 12458207. doi:10.1074/jbc.M211598200 
  31. Kane, Lawrence P; Mollenauer Marianne N, Xu Zheng, Turck Christoph W, Weiss Arthur (Agosto de 2002). «Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription». United States. Mol. Cell. Biol. 22 (16): 5962–74. ISSN 0270-7306. PMC 133991 . PMID 12138205. doi:10.1128/MCB.22.16.5962-5974.2002 
  32. Sarbassov, D D; Guertin David A, Ali Siraj M, Sabatini David M (Fevereiro de 2005). «Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex». United States. Science. 307 (5712): 1098–101. PMID 15718470. doi:10.1126/science.1106148 
  33. Sekulić, A; Hudson C C, Homme J L, Yin P, Otterness D M, Karnitz L M, Abraham R T (Julho de 2000). «A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells». UNITED STATES. Cancer Res. 60 (13): 3504–13. ISSN 0008-5472. PMID 10910062 
  34. Cheng, Susan W Y; Fryer Lee G D, Carling David, Shepherd Peter R (Abril de 2004). «Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status». United States. J. Biol. Chem. 279 (16): 15719–22. ISSN 0021-9258. PMID 14970221. doi:10.1074/jbc.C300534200 
  35. Koh, H; Lee K H, Kim D, Kim S, Kim J W, Chung J (Novembro de 2000). «Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage». UNITED STATES. J. Biol. Chem. 275 (44): 34451–8. ISSN 0021-9258. PMID 10926925. doi:10.1074/jbc.M001753200 
  36. Remy, Ingrid; Michnick Stephen W (Fevereiro de 2004). «Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt». United States. Mol. Cell. Biol. 24 (4): 1493–504. ISSN 0270-7306. PMC 344167 . PMID 14749367. doi:10.1128/MCB.24.4.1493-1504.2004 
  37. Powell, David W; Rane Madhavi J, Chen Qingdan, Singh Saurabh, McLeish Kenneth R (Junho de 2002). «Identification of 14-3-3zeta as a protein kinase B/Akt substrate». United States. J. Biol. Chem. 277 (24): 21639–42. ISSN 0021-9258. PMID 11956222. doi:10.1074/jbc.M203167200 
  38. Ozes, O N; Mayo L D, Gustin J A, Pfeffer S R, Pfeffer L M, Donner D B (Setembro de 1999). «NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase». ENGLAND. Nature. 401 (6748): 82–5. ISSN 0028-0836. PMID 10485710. doi:10.1038/43466 
  39. Romashkova, J A; Makarov S S (Setembro de 1999). «NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling». ENGLAND. Nature. 401 (6748): 86–90. ISSN 0028-0836. PMID 10485711. doi:10.1038/43474 
  40. Fujita, Naoya; Sato Saori, Katayama Kazuhiro, Tsuruo Takashi (Agosto de 2002). «Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization». United States. J. Biol. Chem. 277 (32): 28706–13. ISSN 0021-9258. PMID 12042314. doi:10.1074/jbc.M203668200 

Leitura adicional editar

  • Hemmings BA (1997). «Akt signaling: linking membrane events to life and death decisions.». Science. 275 (5300): 628-30. PMID 9019819 
  • Vanhaesebroeck B, Alessi DR (2000). «The PI3K-PDK1 connection: more than just a road to PKB.». Biochem. J. 346 Pt 3: 561-76. PMID 10698680 
  • Chan TO, Rittenhouse SE, Tsichlis PN (2000). «AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation.». Annu. Rev. Biochem. 68: 965-1014. PMID 10872470. doi:10.1146/annurev.biochem.68.1.965 
  • Pekarsky Y, Hallas C, Croce CM (2001). «Molecular basis of mature T-cell leukemia.». JAMA. 286 (18): 2308-14. PMID 11710897 
  • Dickson LM, Rhodes CJ (2004). «Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt?». Am. J. Physiol. Endocrinol. Metab. 287 (2): E192-8. PMID 15271644. doi:10.1152/ajpendo.00031.2004 
  • Manning BD (2004). «Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis.». J. Cell Biol. 167 (3): 399-403. PMID 15533996. doi:10.1083/jcb.200408161 
  • Shinohara M, Chung YJ, Saji M, Ringel MD (2007). «AKT in thyroid tumorigenesis and progression.». Endocrinology. 148 (3): 942-7. PMID 16946008. doi:10.1210/en.2006-0937