NameActivated CDC42 kinase 1
Synonyms
  • 2.7.10.2
  • ACK-1
  • ACK1
  • Tyrosine kinase non-receptor protein 2
Gene NameTNK2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037072|Activated CDC42 kinase 1
MQPEEGTGWLLELLSEVQLQQYFLRLRDDLNVTRLSHFEYVKNEDLEKIGMGRPGQRRLW
EAVKRRKALCKRKSWMSKVFSGKRLEAEFPPHHSQSTFRKTSPAPGGPAGEGPLQSLTCL
IGEKDLRLLEKLGDGSFGVVRRGEWDAPSGKTVSVAVKCLKPDVLSQPEAMDDFIREVNA
MHSLDHRNLIRLYGVVLTPPMKMVTELAPLGSLLDRLRKHQGHFLLGTLSRYAVQVAEGM
GYLESKRFIHRDLAARNLLLATRDLVKIGDFGLMRALPQNDDHYVMQEHRKVPFAWCAPE
SLKTRTFSHASDTWMFGVTLWEMFTYGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDI
YNVMVQCWAHKPEDRPTFVALRDFLLEAQPTDMRALQDFEEPDKLHIQMNDVITVIEGRA
ENYWWRGQNTRTLCVGPFPRNVVTSVAGLSAQDISQPLQNSFIHTGHGDSDPRHCWGFPD
RIDELYLGNPMDPPDLLSVELSTSRPPQHLGGVKKPTYDPVSEDQDPLSSDFKRLGLRKP
GLPRGLWLAKPSARVPGTKASRGSGAEVTLIDFGEEPVVPALRPCAPSLAQLAMDACSLL
DETPPQSPTRALPRPLHPTPVVDWDARPLPPPPAYDDVAQDEDDFEICSINSTLVGAGVP
AGPSQGQTNYAFVPEQARPPPPLEDNLFLPPQGGGKPPSSAQTAEIFQALQQECMRQLQA
PAGSPAPSPSPGGDDKPQVPPRVPIPPRPTRPHVQLSPAPPGEEETSQWPGPASPPRVPP
REPLSPQGSRTPSPLVPPGSSPLPPRLSSSPGKTMPTTQSFASDPKYATPQVIQAPGPRA
GPCILPIVRDGKKVSSTHYYLLPERPSYLERYQRFLREAQSPEEPTPLPVPLLLPPPSTP
APAAPTATVRPMPQAALDPKANFSTNNSNPGARPPPPRATARLPQRGCPGDGPEAGRPAD
KIQMAMVHGVTTEECQAALQCHGWSVQRAAQYLKVEQLFGLGLRPRGECHKVLEMFDWNL
EQAGCHLLGSWGPAHHKR
Number of residues1038
Molecular Weight114567.605
Theoretical pI7.17
GO Classification
Functions
  • WW domain binding
  • protein tyrosine kinase activity
  • epidermal growth factor receptor binding
  • protein serine/threonine/tyrosine kinase activity
  • ATP binding
  • protein serine/threonine kinase activity
  • hormone receptor binding
  • identical protein binding
  • GTPase inhibitor activity
  • metal ion binding
  • non-membrane spanning protein tyrosine kinase activity
Processes
  • phosphorylation
  • endocytosis
  • cell differentiation
  • cell migration
  • innate immune response
  • regulation of clathrin-mediated endocytosis
  • peptidyl-tyrosine autophosphorylation
  • negative regulation of GTPase activity
  • positive regulation of peptidyl-tyrosine phosphorylation
  • regulation of cell proliferation
  • transmembrane receptor protein tyrosine kinase signaling pathway
  • cell surface receptor signaling pathway
  • small GTPase mediated signal transduction
Components
  • neuronal cell body
  • coated pit
  • cytoplasmic vesicle membrane
  • clathrin-coated vesicle
  • axon
  • extrinsic component of cytoplasmic side of plasma membrane
  • adherens junction
  • cytoplasm
  • membrane
  • nucleus
  • Grb2-EGFR complex
  • dendrite
  • plasma membrane
  • endosome
  • growth cone
General FunctionWw domain binding
Specific FunctionNon-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID8850245
UniProtKB IDQ07912
UniProtKB Entry NameACK1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0016201|Activated CDC42 kinase 1 (TNK2)
ATGCTCGAGGCCCGGCCCCCCAGGACGCAGGGCAGTGACGCTGCCGGTGCCGCTGCGGGG
CGGGGGCTGCGGGCGCTGCTTCTCTCCCTGACCGCAGCCGCTGGGATTTGGGGCTCCATG
GGGGAGAGATCTGCTTACCAGCGCCTGGCTGGGGGCGAGGAGGGACCGCAGAGGCTGGGA
GGCGGCAGAATGCAGCCAGAGGAGGGCACAGGCTGGCTGCTGGAGCTGCTGTCCGAGGTG
CAGCTGCAACAGTACTTCCTGCGGCTCCGAGATGACCTCAACGTCACCCGCCTGTCCCAC
TTTGAGTACGTCAAGAATGAGGACCTGGAGAAGATCGGCATGGGTCGGCCTGGCCAGCGG
CGGCTGTGGGAGGCTGTGAAGAGGAGGAAGGCCTTGTGCAAACGCAAGTCGTGGATGAGT
AAGGTGTTCAGTGGAAAGCGACTGGAGGCTGAGTTCCCACCTCATCACTCTCAGAGCACC
TTCCGGAAGACCTCGCCCGCCCCTGGGGGCCCAGCAGGGGAGGGGCCCCTGCAGAGCCTC
ACCTGCCTCATTGGGGAGAAGGACCTGCGCCTCCTGGAGAAGCTGGGTGATGGTTCCTTT
GGCGTGGTGCGCAGGGGCGAGTGGGACGCGCCCTCAGGGAAGACGGTGAGTGTGGCTGTG
AAGTGCCTGAAGCCCGATGTCCTGAGCCAGCCAGAAGCCATGGACGACTTCATCCGGGAG
GTCAATGCCATGCACTCGCTCGACCACCGAAACCTCATCCGCCTCTACGGGGTGGTGCTC
ACGCCGCCCATGAAGATGGTGACAGAGCTGGCACCTCTGGGATCGTTGTTGGACCGGCTA
CGTAAGCACCAGGGCCACTTCCTCCTGGGGACTCTGAGCCGCTACGCTGTGCAGGTGGCT
GAGGGCATGGGCTACCTGGAGTCCAAGCGCTTTATTCACCGTGACCTGGCTGCCCGCAAT
CTGCTGTTGGCTACCCGCGACCTGGTCAAGATCGGGGACTTTGGGCTGATGCGAGCACTA
CCTCAGAATGACGACCATTACGTCATGCAGGAACATCGCAAGGTGCCCTTCGCCTGGTGT
GCCCCCGAGAGCCTGAAGACACGCACCTTCTCCCATGCCAGCGACACCTGGATGTTCGGG
GTGACACTGTGGGAAATGTTCACCTACGGCCAGGAGCCCTGGATCGGCCTCAACGGCAGT
CAGATCCTGCATAAGATCGACAAGGAGGGGGAGCGGCTGCCCCGGCCCGAGGACTGTCCC
CAGGACATCTACAACGTCATGGTCCAGTGCTGGGCTCACAAGCCAGAGGACAGACCCACG
TTTGTGGCCCTGCGGGACTTCCTGCTGGAGGCCCAGCCCACAGACATGCGGGCCCTTCAG
GACTTTGAGGAACCGGACAAGCTGCACATCCAGATGAATGATGTCATCACCGTCATCGAG
GGAAGGGCCGAGAACTACTGGTGGCGTGGCCAGAACACACGGACGCTGTGTGTGGGGCCC
TTCCCTCGCAACGTGGTGACCTCCGTGGCCGGCCTGTCGGCCCAGGACATCAGCCAGCCC
CTGCAGAACAGCTTCATCCACACAGGGCATGGCGACAGTGACCCCCGCCACTGCTGGGGC
TTCCCGGACAGGATTGACGAACTGTATCTGGGAAACCCCATGGACCCCCCCGACCTCCTG
AGCGTGGAACTGAGCACCTCCCGGCCCCCCCAGCATCTAGGAGGGGTGAAAAGGGAGCCT
CCACCTCGCCCACCTCAGCCTGCCTTCTTCACTCAGAAACCAACCTATGACCCTGTGAGC
GAGGACCAAGACCCCTTGTCCAGCGACTTCAAGAGGCTGGGCCTGCGGAAGCCAGGCCTG
CCCCGAGGGCTGTGGCTGGCGAAGCCCTCGGCGCGGGTGCCGGGCACCAAGGCCAGCCGA
GGCAGCGGGGCTGAGGTCACGCTCATCGACTTCGGTGAGGAGCCCGTGGTCCCGGCCCTA
CGGCCCTGCGCGCCCTCCCTGGCGCAGCTGGCCATGGACGCCTGCTCCCTGCTGGACGAG
ACCCCGCCTCAGAGCCCCACGCGGGCACTGCCCCGGCCCCTGCACCCCACGCCTGTGGTG
GACTGGGACGCACGCCCGCTGCCCCCCCCGCCCGCCTATGACGACGTGGCCCAGGATGAG
GATGACTTTGAGATCTGCTCCATCAACAGCACCCTCGTGGGCGCGGGGGTCCCTGCCGGG
CCCAGCCAGGGCCAGACCAACTACGCCTTTGTGCCTGAGCAGGCGCGGCCGCCCCCTCCC
CTGGAGGACAACCTGTTCCTCCCGCCCCAGGGTGGGGGCAAGCCGCCCAGCTCCGCACAG
ACCGCAGAGATCTTCCAGGCGCTACAGCAGGAGTGCATGAGGCAACTGCAGGCTCCGGCC
GGCTCCCCGGCCCCCTCTCCCAGCCCGGGGGGTGACGACAAGCCCCAGGTGCCTCCTCGG
GTACCCATCCCCCCTCGGCCCACGCGCCCACACGTCCAGCTGTCTCCAGCCCCCCCGGGC
GAGGAGGAGACCAGCCAGTGGCCTGGACCTGCTTCCCCTCCCCGGGTGCCTCCGCGGGAG
CCCCTGTCCCCTCAAGGCTCGAGGACACCCAGCCCCCTGGTACCACCTGGCAGCTCCCCG
CTGCCACCCCGGCTCTCAAGCTCACCTGGGAAGACCATGCCCACCACCCAGAGCTTTGCC
TCAGACCCCAAGTACGCCACCCCCCAGGTGATCCAGGCCCCTGGCCCGCGGGCTGGTCCC
TGCATCCTGCCCATCGTCCGGGATGGCAAGAAGGTCAGCAGCACCCACTATTACTTGCTG
CCCGAGCGACCATCCTACCTGGAGCGCTACCAGCGCTTCCTGCGTGAGGCCCAGAGCCCC
GAGGAGCCTACCCCCCTGCCTGTGCCTCTGCTGCTGCCCCCACCCAGCACCCCAGCCCCC
GCCGCCCCCACGGCCACCGTGCGGCCGATGCCCCAGGCTGCCTTGGACCCCAAGGCCAAC
TTCTCCACCAACAACAGCAACCCAGGGGCCCGGCCACCACCCCCGAGGGCCACTGCTCGG
CTGCCACAGAGGGGCTGCCCTGGCGATGGGCCAGAGGCGGGCCGGCCAGCAGACAAGATC
CAGATGGTGGAGCAGCTCTTCGGGCTGGGTCTGCGGCCCAGAGGGGAGTGCCACAAAGTG
CTGGAGATGTTCGACTGGAACCTGGAGCAGGCCGGCTGCCACCTTCTGGGCTCCTGGGGC
CCTGCCCACCACAAGCGCTGA
GenBank Gene IDL13738
GeneCard IDNot Available
GenAtlas IDTNK2
HGNC IDHGNC:19297
Chromosome Location3
Locus3q29
References
  1. Manser E, Leung T, Salihuddin H, Tan L, Lim L: A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42. Nature. 1993 May 27;363(6427):364-7. 8497321
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  3. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. 16641997
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Eisenmann KM, McCarthy JB, Simpson MA, Keely PJ, Guan JL, Tachibana K, Lim L, Manser E, Furcht LT, Iida J: Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nat Cell Biol. 1999 Dec;1(8):507-13. 10587647
  6. Kato J, Kaziro Y, Satoh T: Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation. Biochem Biophys Res Commun. 2000 Feb 5;268(1):141-7. 10652228
  7. Teo M, Tan L, Lim L, Manser E: The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors. J Biol Chem. 2001 May 25;276(21):18392-8. Epub 2001 Feb 27. 11278436
  8. Ahmed I, Calle Y, Sayed MA, Kamal JM, Rengaswamy P, Manser E, Meiners S, Nur-E-Kamal A: Cdc42-dependent nuclear translocation of non-receptor tyrosine kinase, ACK. Biochem Biophys Res Commun. 2004 Feb 6;314(2):571-9. 14733946
  9. Mahajan NP, Whang YE, Mohler JL, Earp HS: Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res. 2005 Nov 15;65(22):10514-23. 16288044
  10. Yeow-Fong L, Lim L, Manser E: SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1. FEBS Lett. 2005 Sep 12;579(22):5040-8. 16137687
  11. Yokoyama N, Lougheed J, Miller WT: Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase. J Biol Chem. 2005 Dec 23;280(51):42219-26. Epub 2005 Oct 28. 16257963
  12. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  13. van der Horst EH, Degenhardt YY, Strelow A, Slavin A, Chinn L, Orf J, Rong M, Li S, See LH, Nguyen KQ, Hoey T, Wesche H, Powers S: Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15901-6. Epub 2005 Oct 24. 16247015
  14. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  15. Modzelewska K, Newman LP, Desai R, Keely PJ: Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. 17038317
  16. Yokoyama N, Miller WT: Purification and enzyme activity of ACK1. Methods Enzymol. 2006;406:250-60. 16472662
  17. Mahajan NP, Liu Y, Majumder S, Warren MR, Parker CE, Mohler JL, Earp HS, Whang YE: Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8438-43. Epub 2007 May 9. 17494760
  18. Eley L, Moochhala SH, Simms R, Hildebrandt F, Sayer JA: Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct. Biochem Biophys Res Commun. 2008 Jul 11;371(4):877-82. doi: 10.1016/j.bbrc.2008.05.016. Epub 2008 May 12. 18477472
  19. Howlin J, Rosenkvist J, Andersson T: TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells. Breast Cancer Res. 2008;10(2):R36. doi: 10.1186/bcr2087. Epub 2008 Apr 24. 18435854
  20. Grovdal LM, Johannessen LE, Rodland MS, Madshus IH, Stang E: Dysregulation of Ack1 inhibits down-regulation of the EGF receptor. Exp Cell Res. 2008 Apr 1;314(6):1292-300. doi: 10.1016/j.yexcr.2007.12.017. Epub 2008 Jan 5. 18262180
  21. 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. 18691976
  22. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  23. Chan W, Tian R, Lee YF, Sit ST, Lim L, Manser E: Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. J Biol Chem. 2009 Mar 20;284(12):8185-94. doi: 10.1074/jbc.M806877200. Epub 2009 Jan 14. 19144635
  24. Pao-Chun L, Chan PM, Chan W, Manser E: Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub 2009 Oct 8. 19815557
  25. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  26. Prieto-Echague V, Gucwa A, Brown DA, Miller WT: Regulation of Ack1 localization and activity by the amino-terminal SAM domain. BMC Biochem. 2010 Oct 27;11:42. doi: 10.1186/1471-2091-11-42. 20979614
  27. Liu Y, Karaca M, Zhang Z, Gioeli D, Earp HS, Whang YE: Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases. Oncogene. 2010 Jun 3;29(22):3208-16. doi: 10.1038/onc.2010.103. Epub 2010 Apr 12. 20383201
  28. Mahajan K, Coppola D, Challa S, Fang B, Chen YA, Zhu W, Lopez AS, Koomen J, Engelman RW, Rivera C, Muraoka-Cook RS, Cheng JQ, Schonbrunn E, Sebti SM, Earp HS, Mahajan NP: Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation. PLoS One. 2010 Mar 19;5(3):e9646. doi: 10.1371/journal.pone.0009646. 20333297
  29. Mahajan K, Challa S, Coppola D, Lawrence H, Luo Y, Gevariya H, Zhu W, Chen YA, Lawrence NJ, Mahajan NP: Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity. Prostate. 2010 Sep 1;70(12):1274-85. doi: 10.1002/pros.21163. 20623637
  30. Chan W, Sit ST, Manser E: The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation. Biochem J. 2011 Apr 15;435(2):355-64. doi: 10.1042/BJ20102156. 21309750
  31. Shen H, Ferguson SM, Dephoure N, Park R, Yang Y, Volpicelli-Daley L, Gygi S, Schlessinger J, De Camilli P: Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin. Mol Biol Cell. 2011 Feb 15;22(4):493-502. doi: 10.1091/mbc.E10-07-0637. Epub 2010 Dec 17. 21169560
  32. Mahajan K, Mahajan NP: Shepherding AKT and androgen receptor by Ack1 tyrosine kinase. J Cell Physiol. 2010 Aug;224(2):327-33. doi: 10.1002/jcp.22162. 20432460
  33. Mott HR, Owen D, Nietlispach D, Lowe PN, Manser E, Lim L, Laue ED: Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. Nature. 1999 May 27;399(6734):384-8. 10360579
  34. Lougheed JC, Chen RH, Mak P, Stout TJ: Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1. J Biol Chem. 2004 Oct 15;279(42):44039-45. Epub 2004 Aug 11. 15308621
  35. Kopecky DJ, Hao X, Chen Y, Fu J, Jiao X, Jaen JC, Cardozo MG, Liu J, Wang Z, Walker NP, Wesche H, Li S, Farrelly E, Xiao SH, Kayser F: Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6352-6. doi: 10.1016/j.bmcl.2008.10.092. Epub 2008 Nov 1. 18993068
  36. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846