The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TNK2  -  tyrosine kinase, non-receptor, 2

Homo sapiens

Synonyms: ACK, ACK-1, ACK1, Activated CDC42 kinase 1, Tyrosine kinase non-receptor protein 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TNK2 or Ack1 [1]

  • Ack1 activation has been reported in prostate [2] [3], breast [4] and pancreatic [5] primary human tumors. Levels of phosphorylated Ack1 correlated with disease progression and inversely correlated with patient survival.
  • Somatic mutations in Ack1 have been identified in lung (R34L), ovarian (R99Q, E346K) and stomach (M409I) cancers [4].
  • Transgenic mice expressing activated Ack1 specifically in prostates developed prostatic intraepithelial neoplasia (PINs) in about 40 weeks [4].
  • Ack1 specific small molecule inhibitor, AIM-100 inhibited growth of various cancer derived cell lines [6] and arrested cells in G1 phase of cell cycle [7].
  • Ack1 gene amplification has been observed in breast, lung and prostate cancers [8].
  • Overexpression of Ack1 in cancer cell lines increased the invasive phenotype of these cells and leads to increased mortality in a mouse model of metastasis [8]
  • Because tyrosine kinase activity is a requirement for neuritogenesis in several cell systems, we investigated whether endogenous mAChRs (principally of the M3 subtype) expressed in human SH-SY5Y neuroblastoma cells would signal to ACK-1 [9].
  • ACK-1 phosphorylation was blocked by Clostridium difficile toxin B, an inhibitor of Rho family GTPases [9].
  • Further, these findings suggest that Ack1 could be a novel therapeutic target for prostate cancer [10].
  • To characterize the enzymatic properties of ACK, we have expressed and purified active ACK using the baculovirus/Sf9 cell system [11].
  • Targeting the Ack1 kinase may be a potential therapeutic strategy in prostate cancer [3].

Psychiatry related information on TNK2


High impact information on TNK2

  • The interaction extends the beta-sheet in Cdc42 by binding an extended strand from ACK, as seen in Ras/effector interactions, but it also involves other regions of the G protein that are important for determining the specificity of effector binding [13].
  • Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK [13].
  • Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1 [8].
  • Biochemical studies show that Ack1 is involved in extracellular matrix-induced integrin signaling, ultimately activating signaling processes like the activation of the small GTPase Rac [8].
  • Site-directed mutagenesis revealed that activated Ack1 primarily phosphorylated Wwox at Tyr287, suggesting that phosphorylation of distinct tyrosine residues activate or degrade Wwox [10].

Chemical compound and disease context of TNK2

  • Specifically, we evaluated the Alcohol/Drug Problem Acknowledgment scale (ACK; Weed, Butcher, & Williams, 1994), the Alcohol/Drug Problem Proneness scale (PRO; Weed et al., 1994), and the MacAndrew Alcoholism Scale-Revised (MAC-R; Butcher et al., 1992) in the prediction of substance abuse [12].

Biological context of TNK2


Anatomical context of TNK2


Associations of TNK2 with chemical compounds


Regulatory relationships of TNK2

  • Signaling through this complex is functionally relevant, because treatment with either p130(Cas) or Ack1 siRNA blocked Cdc42-induced migration [22].
  • The interplay between Nedd4-2-related E3 ligases that regulate ACK1 levels and Cbl that modifies EGF receptor impinges on cell receptor dynamics [23].

Other interactions of TNK2

  • Here we show the induction of tyrosine phosphorylation of ACK in response to temperature shift-down to 25 degrees C, and hypertonic shock, as well as stimulation with epidermal growth factor (EGF) in human embryonic kidney (HEK) 293 cells [14].
  • A non-receptor tyrosine kinase ACK, which specifically binds to the GTP-bound form of Cdc42, was isolated as a putative target of Cdc42 [14].
  • Therefore, the activation of ACK1 and subsequent downstream signaling require both Cdc42-dependent and Grb2-dependent processes within the cell [18].
  • On the other hand, replacement of the corresponding region of TC10 with the AB region enabled TC10 to acquire ACK-binding ability [24].
  • GEF activity of Ras-GRF1 toward Ha-Ras, as defined by in vitro GDP binding and release assays, was augmented after tyrosine phosphorylation by ACK1 [17].

Analytical, diagnostic and therapeutic context of TNK2

  • PBL obtained by leukapheresis were subjected to NH4Cl (ACK) treatment to clear erythrocyte contamination; Ficoll separation was not performed [25].



  1. Shepherding AKT and androgen receptor by Ack1 tyrosine kinase. Mahajan, K., Mahajan, N.P. J. Cell. Physiol. (2010) [Pubmed]
  2. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Mahajan, N.P., Whang, Y.E., Mohler, J.L., Earp, H.S. Cancer. Res. (2005) [Pubmed]
  3. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Mahajan, N.P., Liu, Y., Majumder, S., Warren, M.R., Parker, C.E., Mohler, J.L., Earp, H.S., Whang, Y.E. Proc. Natl. Acad. Sci. U. S. A. (2007) [Pubmed]
  4. Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation. Mahajan, K., Coppola, D., Challa, S., Fang, B., Chen, Y.A., Zhu, W., Lopez, A.S., Koomen, J., Engelman, R.W., Rivera, C., Muraoka-Cook, R.S., Cheng, J.Q., Schönbrunn, E., Sebti, S.M., Earp, H.S., Mahajan, N.P. PLoS. One. (2010) [Pubmed]
  5. Ack1 tyrosine kinase activation correlates with pancreatic cancer progression. Mahajan, K., Coppola, D., Chen, Y.A., Zhu, W., Lawrence, H.R., Lawrence, N.J., Mahajan, N.P. Am. J. Pathol. (2012) [Pubmed]
  6. Ack1 mediated androgen receptor phosphorylation modulates radiation resistance in castration resistant prostate cancer. Mahajan, K., Coppola, D., Rawal, B., Chen, Y.A., Lawrence, H.R., Engelman, R.W., Lawrence, N.J., Mahajan, N.P. J. Biol. Chem. (2012) [Pubmed]
  7. Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity. Mahajan, K., Challa, S., Coppola, D., Lawrence, H., Luo, Y., Gevariya, H., Zhu, W., Chen, Y.A., Lawrence, N.J., Mahajan, N.P. Prostate. (2010) [Pubmed]
  8. Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1. van der Horst, E.H., Degenhardt, Y.Y., Strelow, A., Slavin, A., Chinn, L., Orf, J., Rong, M., Li, S., See, L.H., Nguyen, K.Q., Hoey, T., Wesche, H., Powers, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway. Linseman, D.A., Heidenreich, K.A., Fisher, S.K. J. Biol. Chem. (2001) [Pubmed]
  10. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Mahajan, N.P., Whang, Y.E., Mohler, J.L., Earp, H.S. Cancer Res. (2005) [Pubmed]
  11. Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck. Yokoyama, N., Miller, W.T. J. Biol. Chem. (2003) [Pubmed]
  12. Use of the MMPI-A to detect substance abuse in a juvenile correctional setting. Stein, L.A., Graham, J.R. Journal of personality assessment. (2001) [Pubmed]
  13. Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. Mott, H.R., Owen, D., Nietlispach, D., Lowe, P.N., Manser, E., Lim, L., Laue, E.D. Nature (1999) [Pubmed]
  14. Tyrosine phosphorylation of ACK in response to temperature shift-down, hyperosmotic shock, and epidermal growth factor stimulation. Satoh, T., Kato, J., Nishida, K., Kaziro, Y. FEBS Lett. (1996) [Pubmed]
  15. SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1. Yeow-Fong, L., Lim, L., Manser, E. FEBS Lett. (2005) [Pubmed]
  16. Cdc42-dependent nuclear translocation of non-receptor tyrosine kinase, ACK. Ahmed, I., Calle, Y., Sayed, M.A., Kamal, J.M., Rengaswamy, P., Manser, E., Meiners, S., Nur-E-Kamal, A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  17. Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1. Kiyono, M., Kato, J., Kataoka, T., Kaziro, Y., Satoh, T. J. Biol. Chem. (2000) [Pubmed]
  18. Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner. Kato-Stankiewicz, J., Ueda, S., Kataoka, T., Kaziro, Y., Satoh, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  19. A subset of CD16-natural killer cells without antibody-dependent cellular cytotoxicity function. Schubert, J., Heiken, H., Jacobs, R., Delany, P., Witte, T., Schmidt, R.E. Nat. Immun. Cell Growth Regul. (1990) [Pubmed]
  20. The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors. Teo, M., Tan, L., Lim, L., Manser, E. J. Biol. Chem. (2001) [Pubmed]
  21. Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation. Kato, J., Kaziro, Y., Satoh, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  22. Ack1 Mediates Cdc42-dependent Cell Migration and Signaling to p130Cas. Modzelewska, K., Newman, L.P., Desai, R., Keely, P.J. J. Biol. Chem. (2006) [Pubmed]
  23. Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. Chan, W., Tian, R., Lee, Y.F., Sit, S.T., Lim, L., Manser, E. J. Biol. Chem. (2009) [Pubmed]
  24. Identification of the region in Cdc42 that confers the binding specificity to activated Cdc42-associated kinase. Gu, Y., Lin, Q., Childress, C., Yang, W. J. Biol. Chem. (2004) [Pubmed]
  25. A new procedure for large scale production and freezing of lymphokine activated killer (LAK) cells to be used in adoptive immunotherapy of cancer. Gambacorti-Passerini, C., Radrizzani, M., Rivoltini, L., Marchesi, E., Ravagnani, F., Sciorelli, G., Cascinelli, N., Parmiani, G. Tumori. (1988) [Pubmed]
WikiGenes - Universities