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PTK6  -  protein tyrosine kinase 6

Homo sapiens

Synonyms: BRK, Breast tumor kinase, Protein-tyrosine kinase 6, Tyrosine-protein kinase BRK
 
 
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Disease relevance of PTK6

 

High impact information on PTK6

  • By using an in vitro cytotoxicity assay with NIH 3T3 and Fisher BRK-derived cells expressing exogenously introduced oncogenes, we found that adenovirus E1A proteins induce susceptibility to TNF killing [6].
  • Sam68 enhances the cytoplasmic utilization of intron-containing RNA and is functionally regulated by the nuclear kinase Sik/BRK [7].
  • Expression and Oncogenic Role of Brk (PTK6/Sik) Protein Tyrosine Kinase in Lymphocytes [8].
  • A recombinant PTK6 Kinase domain connected to the Linker region had catalytic activity in terms of autophosphorylation, phosphorylation of a PTK6 substrate, BKS, and phosphorylation of an oligopeptide substrate, whereas the Kinase domain itself, or one connected to a Linker region containing a W184A substitution, did not [9].
  • Protein-tyrosine kinase-6 (PTK6, also known as Brk) is a non-receptor tyrosine kinase that contains SH3, SH2, and catalytic (Kinase) domains [9].
 

Chemical compound and disease context of PTK6

 

Biological context of PTK6

  • The introduction of the W184A mutation into PTK6 also abrogated autophosphorylation and phosphorylation of another PTK6 substrate, Sam68, as well as phosphorylation of intracellular proteins [9].
  • It also abolished the ability of PTK6 to promote proliferation and prevent apoptosis of HEK 293 cells, as well as to permit anchorage-independent colony formation [9].
  • The solution structure clearly indicates that the SH2 domain of human PTK6 contains a consensus alpha/beta-fold and a Tyr(P) peptide binding surface, which are common to other SH2 domains [1].
  • The human protein tyrosine kinase-6 (PTK6) polypeptide that is deduced from the cDNA sequence contains a Src homology (SH) 3 domain, SH2 domain, and catalytic domain of tyrosine kinase [12].
  • The 813-bp 5'-flanking sequence of the PTK6 gene upstream of a luciferase reporter gene conferred significant promoter activity, at approximately 60% level of the SV40 promoter, in transient expression assays into MCF-7, human breast tumor cell line [13].
 

Anatomical context of PTK6

 

Associations of PTK6 with chemical compounds

  • This effect of BRK on the regulation of phosphoinositide 3-kinase and Akt activity may account for BRK's ability to enhance mammary cell mitogenesis, and raises the possibility that breast tumours expressing BRK may acquire a resistance to pro-apoptotic signals [15].
  • CONCLUSIONS: The in vivo distribution of BRK and its up-regulation during in vitro differentiation of HaCaT cells, together with the activation of its kinase activity by calcium/ionomycin and its influence on K10 expression, all indicate a role for BRK in the complex process of keratinocyte differentiation [16].
 

Enzymatic interactions of PTK6

  • In addition, BKS recruited an unidentified 100 kDa protein that was also phosphorylated on tyrosine residues in the presence of BRK [17].
 

Regulatory relationships of PTK6

 

Other interactions of PTK6

 

Analytical, diagnostic and therapeutic context of PTK6

References

  1. Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain. Hong, E., Shin, J., Kim, H.I., Lee, S.T., Lee, W. J. Biol. Chem. (2004) [Pubmed]
  2. Characterization of the 5'-flanking region of the human PTK6 gene. Kang, K.N., Kim, M., Pae, K.M., Lee, S.T. Biochim. Biophys. Acta (2002) [Pubmed]
  3. Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma. Easty, D.J., Mitchell, P.J., Patel, K., Flørenes, V.A., Spritz, R.A., Bennett, D.C. Int. J. Cancer (1997) [Pubmed]
  4. BRK/Sik expression in the gastrointestinal tract and in colon tumors. Llor, X., Serfas, M.S., Bie, W., Vasioukhin, V., Polonskaia, M., Derry, J., Abbott, C.M., Tyner, A.L. Clin. Cancer Res. (1999) [Pubmed]
  5. Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Derry, J.J., Prins, G.S., Ray, V., Tyner, A.L. Oncogene (2003) [Pubmed]
  6. Induction by E1A oncogene expression of cellular susceptibility to lysis by TNF. Chen, M.J., Holskin, B., Strickler, J., Gorniak, J., Clark, M.A., Johnson, P.J., Mitcho, M., Shalloway, D. Nature (1987) [Pubmed]
  7. Sam68 enhances the cytoplasmic utilization of intron-containing RNA and is functionally regulated by the nuclear kinase Sik/BRK. Coyle, J.H., Guzik, B.W., Bor, Y.C., Jin, L., Eisner-Smerage, L., Taylor, S.J., Rekosh, D., Hammarskjöld, M.L. Mol. Cell. Biol. (2003) [Pubmed]
  8. Expression and Oncogenic Role of Brk (PTK6/Sik) Protein Tyrosine Kinase in Lymphocytes. Kasprzycka, M., Majewski, M., Wang, Z.J., Ptasznik, A., Wysocka, M., Zhang, Q., Marzec, M., Gimotty, P., Crompton, M.R., Wasik, M.A. Am. J. Pathol. (2006) [Pubmed]
  9. An intramolecular interaction between SH2-kinase linker and kinase domain is essential for the catalytic activity of protein-tyrosine kinase-6. Kim, H.I.e., Lee, S.T. J. Biol. Chem. (2005) [Pubmed]
  10. Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression. Lukong, K.E., Larocque, D., Tyner, A.L., Richard, S. J. Biol. Chem. (2005) [Pubmed]
  11. Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis. Zhao, C., Yasui, K., Lee, C.J., Kurioka, H., Hosokawa, Y., Oka, T., Inazawa, J. Cancer (2003) [Pubmed]
  12. Purification and spectroscopic characterization of the human protein tyrosine kinase-6 SH3 domain. Koo, B.K., Kim, M.H., Lee, S.T., Lee, W. J. Biochem. Mol. Biol. (2002) [Pubmed]
  13. Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase. Lee, H., Kim, M., Lee, K.H., Kang, K.N., Lee, S.T. Mol. Cells (1998) [Pubmed]
  14. Regulated association of protein kinase B/Akt with breast tumor kinase. Zhang, P., Ostrander, J.H., Faivre, E.J., Olsen, A., Fitzsimmons, D., Lange, C.A. J. Biol. Chem. (2005) [Pubmed]
  15. Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation. Kamalati, T., Jolin, H.E., Fry, M.J., Crompton, M.R. Oncogene (2000) [Pubmed]
  16. Role of breast tumour kinase in the in vitro differentiation of HaCaT cells. Wang, T.C., Jee, S.H., Tsai, T.F., Huang, Y.L., Tsai, W.L., Chen, R.H. Br. J. Dermatol. (2005) [Pubmed]
  17. A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK. Mitchell, P.J., Sara, E.A., Crompton, M.R. Oncogene (2000) [Pubmed]
  18. Simultaneous over-expression of the Her2/neu and PTK6 tyrosine kinases in archival invasive ductal breast carcinomas. Born, M., Quintanilla-Fend, L., Braselmann, H., Reich, U., Richter, M., Hutzler, P., Aubele, M. J. Pathol. (2005) [Pubmed]
  19. Assignment of the human PTK6 gene encoding a non-receptor protein tyrosine kinase to 20q13.3 by fluorescence in situ hybridization. Park, S.H., Lee, K.H., Kim, H., Lee, S.T. Cytogenet. Cell Genet. (1997) [Pubmed]
  20. Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium. Petro, B.J., Tan, R.C., Tyner, A.L., Lingen, M.W., Watanabe, K. Oral Oncol. (2004) [Pubmed]
 
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