Aktivirana CDC42 kinaza 1, takođe poznata kao ACK1, je enzim koji je kod ljudi kodiran TNK2genom.[1][2][3][4][5]
TNK2 gen kodira nereceptorsku tirozinsku kinazu, ACK1, koja se vezuje za višestruke receptorske tirozinske kinaze e.g. EGFR, MERTK, AXL, HER2 i insulinski receptor (IR). ACK1 takođe interaguje sa Cdc42Hs u njegovoj GTP-vezanoj formi i inhibira intrinzičnu i GTPaznu aktivnost Cdc42H. Vezivanje je posredovano jedistvenom sekvencom od 47 aminokiselina između C-terminusa i SH3 domena. Ovaj protein učestvuje u regulatornom mehanizmu kojim se održava GTP-vezana aktivna forma Cdc42H i koji je direktno povezan sa torozinsko fosforilacionim putem prenosa signala. Poznato je nekoliko alternativno splajsovanih transkriptnih varijanti ovog gena, ali se izražavaju samo dve varijante.[5]
ACK1 ili TNK2 formira interakcije sa AKT,[3] Androgenskim receptorom ili AR,[6] tumornim supresorom WWOX,[7]FYN[8] i Grb2.[9][10] ACK1 interakcije sa njegovim supstratima dovode do njihove fosforilacije na specifičnim tirozinskim ostacima. ACK1 direktno fosforiliše AKT na tirozinu 176, AR na tirosizinima 267 i 363, i WWOX na torozinu 287. Ack1-AR signalizacije takođe učestvuje u regulaciji ATM nivoaa[11]
↑Manser E, Leung T, Salihuddin H, Tan L, Lim L (June 1993). „A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42”. Nature363 (6427): 364–7. DOI:10.1038/363364a0. PMID8497321.
↑Yokoyama N, Miller WT (November 2003). „Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck”. J Biol Chem278 (48): 47713–23. DOI:10.1074/jbc.M306716200. PMID14506255.
↑Mahajan NP, Liu Y, Majumder S, Warren MR, Parker CE, Mohler JL, Earp HS, Whang YE. (May 2007). „Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation.”. Proc Natl Acad Sci U S A.104 (20): 8438–43. DOI:10.1073/pnas.0700420104. PMID17494760.
↑Mahajan NP, Whang YE, Mohler JL, Earp HS. (November 2005). „Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox.”. Cancer Res.65 (22): 10514–23. DOI:10.1158/0008-5472.can-05-1127. PMID16288044.
↑Linseman DA, Heidenreich KA, Fisher SK (February 2001). „Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway”. J. Biol. Chem.276 (8): 5622–8. DOI:10.1074/jbc.M006812200. PMID11087735.
↑Satoh T, Kato J, Nishida K, Kaziro Y (May 1996). „Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation”. FEBS Lett.386 (2-3): 230–4. DOI:10.1016/0014-5793(96)00449-8. PMID8647288.
↑Kato-Stankiewicz J, Ueda S, Kataoka T, Kaziro Y, Satoh T (June 2001). „Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner”. Biochem. Biophys. Res. Commun.284 (2): 470–7. DOI:10.1006/bbrc.2001.5004. PMID11394904.
↑Mahajan K, Coppola D, Rawal B, Chen YA, Lawrence HR, Engelman RW, Lawrence NJ, Mahajan NP. (June 2012). „Ack1-mediated androgen receptor phosphorylation modulates radiation resistance in castration-resistant prostate cancer.”. J Biol Chem.287 (26): 22112–22. DOI:10.1074/jbc.M112.357384. PMID22566699.
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Satoh T, Kato J, Nishida K, Kaziro Y (1996). „Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation”. FEBS Lett.386 (2–3): 230–4. DOI:10.1016/0014-5793(96)00449-8. PMID8647288.
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Linseman DA, Heidenreich KA, Fisher SK (2001). „Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway”. J. Biol. Chem.276 (8): 5622–8. DOI:10.1074/jbc.M006812200. PMID11087735.
Teo M, Tan L, Lim L, Manser E (2001). „The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors”. J. Biol. Chem.276 (21): 18392–8. DOI:10.1074/jbc.M008795200. PMID11278436.
Kato-Stankiewicz J, Ueda S, Kataoka T, et al. (2001). „Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner”. Biochem. Biophys. Res. Commun.284 (2): 470–7. DOI:10.1006/bbrc.2001.5004. PMID11394904.
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