Protein Tyrosine Kinase 6 (PTK6)

BRK; Breast tumor kinase; Tyrosine-protein kinase BRK

SPN	S502
HGNC	9617
MGI	99683
PubMed	23928995
RGD	1309098
UniProt	Q13882
Wiki	PTK6

Tyrosine-protein kinase 6 is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. The encoded protein has been shown to undergo autophosphorylation.

The deduced 451-amino acid polypeptide sequence was composed of 3 domains: an SH3 domain, an SH2 domain, and a catalytic domain. The sequence of BRK, unlike that of SRC, does not include an N-terminal myristoylation domain.

Reference

"Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours."
Oncogene 9:2383-2390(1994) [PubMed] [Europe PMC] [Abstract]

"Characterisation and chromosome mapping of the human non receptor tyrosine kinase gene, brk."
Oncogene 15:1497-1502(1997) [PubMed] [Europe PMC] [Abstract]

"Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase."
Mol. Cells 8:401-407(1998) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 20."
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor."
J. Biol. Chem. 271:30956-30963(1996) [PubMed] [Europe PMC] [Abstract]

"Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma."
Int. J. Cancer 71:1061-1065(1997) [PubMed] [Europe PMC] [Abstract]

"A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK."
Oncogene 19:4273-4282(2000) [PubMed] [Europe PMC] [Abstract]

"Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability."
Mol. Cell. Biol. 20:6114-6126(2000) [PubMed] [Europe PMC] [Abstract]

"Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition."
J. Biol. Chem. 277:34634-34641(2002) [PubMed] [Europe PMC] [Abstract]

"Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells."
Oncogene 22:4212-4220(2003) [PubMed] [Europe PMC] [Abstract]

"The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2."
J. Biol. Chem. 279:54398-54404(2004) [PubMed] [Europe PMC] [Abstract]

"Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin."
Mol. Cell. Biol. 24:10558-10572(2004) [PubMed] [Europe PMC] [Abstract]

"Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium."
Oral Oncol. 40:1040-1047(2004) [PubMed] [Europe PMC] [Abstract]

"Regulated association of protein kinase B/Akt with breast tumor kinase."
J. Biol. Chem. 280:1982-1991(2005) [PubMed] [Europe PMC] [Abstract]

"An intramolecular interaction between SH2-kinase linker and kinase domain is essential for the catalytic activity of protein-tyrosine kinase-6."
J. Biol. Chem. 280:28973-28980(2005) [PubMed] [Europe PMC] [Abstract]

"Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression."
J. Biol. Chem. 280:38639-38647(2005) [PubMed] [Europe PMC] [Abstract]

"Interaction between Brk kinase and insulin receptor substrate-4."
Oncogene 24:5656-5664(2005) [PubMed] [Europe PMC] [Abstract]

"Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes."
Am. J. Pathol. 168:1631-1641(2006) [PubMed] [Europe PMC] [Abstract]

"Identification of STAT3 as a specific substrate of breast tumor kinase."
Oncogene 25:4904-4912(2006) [PubMed] [Europe PMC] [Abstract]

"Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6."
Biochem. Biophys. Res. Commun. 362:829-834(2007) [PubMed] [Europe PMC] [Abstract]

"Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6."
Breast Cancer Res. 9:R79-R79(2007) [PubMed] [Europe PMC] [Abstract]

"Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion."
Cancer Res. 68:7779-7787(2008) [PubMed] [Europe PMC] [Abstract]

"Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma."
Mol. Cancer Res. 6:383-394(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"Brk is coamplified with ErbB2 to promote proliferation in breast cancer."
Proc. Natl. Acad. Sci. U.S.A. 105:12463-12468(2008) [PubMed] [Europe PMC] [Abstract]

"BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest."
Cell. Signal. 21:1415-1422(2009) [PubMed] [Europe PMC] [Abstract]

"Building a better understanding of the intracellular tyrosine kinase PTK6 - BRK by BRK."
Biochim. Biophys. Acta 1806:66-73(2010) [PubMed] [Europe PMC] [Abstract]

"Identification of beta-catenin as a target of the intracellular tyrosine kinase PTK6."
J. Cell Sci. 123:236-245(2010) [PubMed] [Europe PMC] [Abstract]

"The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of beta-catenin."
PLoS ONE 6:E14789-E14789(2011) [PubMed] [Europe PMC] [Abstract]

"Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain."
J. Biol. Chem. 279:29700-29708(2004) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]