title: PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.
abstract: Protein Tyrosine kinase 6 (PTK6/BRK) is overexpressed in the majority of human breast tumors and breast tumor cell lines. It is also expressed in normal epithelial linings of the gastrointestinal tract, skin, and prostate. To date, expression of PTK6 has not been extensively examined in the normal human mammary gland. We detected PTK6 mRNA and protein expression in the immortalized normal MCF-10A human mammary gland epithelial cell line, and examined PTK6 expression and activation in a normal human breast tissue microarray, as well as in human breast tumors. Phosphorylation of tyrosine residue 342 in the PTK6 activation loop corresponds with its activation. Similar to findings in the prostate, we detect nuclear and cytoplasmic PTK6 in normal mammary gland epithelial cells, but no phosphorylation of tyrosine residue 342. However, in human breast tumors, striking PTK6 expression and phosphorylation of tyrosine 342 is observed at the plasma membrane. PTK6 is expressed in the normal human mammary gland, but does not appear to be active and may have kinase-independent functions that are distinct from its cancer promoting activities at the membrane. Understanding consequences of PTK6 activation at the plasma membrane may have implications for developing novel targeted therapies against this kinase.
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago IL.
authors.forename: Maoyu
authors.initials: M
authors.lastname: Peng
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago IL.
authors.forename: Rajyasree
authors.initials: R
authors.lastname: Emmadi
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago IL.
authors.forename: Zebin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago IL.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Wiley
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago IL.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Gann
authors.affiliation: Department of Surgery, Northwestern Feinberg School of Medicine, Chicago, IL.
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Allina Health, Minneapolis, MN, USA.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Banerji
authors.affiliation: Allina Health, Minneapolis, MN, USA.
authors.forename: William
authors.initials: W
authors.lastname: McDonald
authors.affiliation: Department of Biopharmaceutical Sciences University of Illinois at Chicago, Chicago IL.
authors.forename: Szilard
authors.initials: S
authors.lastname: Asztalos
authors.affiliation: Department of Biopharmaceutical Sciences University of Illinois at Chicago, Chicago IL.
authors.forename: Thao N D
authors.initials: TN
authors.lastname: Pham
authors.affiliation: Department of Biopharmaceutical Sciences University of Illinois at Chicago, Chicago IL.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Tonetti
authors.affiliation: Departments of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago IL.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Tyner
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000201:enzymology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human