title: Epidermal growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers.
abstract: Epidermal growth factor receptor (EGFR) initiates a signaling cascade that leads to DNA synthesis and cell proliferation, but its role in regulating DNA replication licensing is unclear. Here, we show that activated EGFR phosphorylates the p56 isoform of Lyn, p56(Lyn), at Y32, which then phosphorylates MCM7, a licensing factor critical for DNA replication, at Y600 to increase its association with other minichromosome maintenance complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Both p56(Lyn) Y32 and MCM7 Y600 phosphorylation are enhanced in proliferating cells and correlated with poor survival of breast cancer patients. These results establish a signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells.
authors.affiliation: Department of Molecular and Cellular Oncology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Huang
authors.forename: Longfei
authors.initials: L
authors.lastname: Huo
authors.forename: Ying-Nai
authors.initials: YN
authors.lastname: Wang
authors.forename: Weiya
authors.initials: W
authors.lastname: Xia
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Wei
authors.forename: Shih-Shin
authors.initials: SS
authors.lastname: Chang
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Chang
authors.forename: Yueh-Fu
authors.initials: YF
authors.lastname: Fang
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Chen
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Lang
authors.forename: Chun
authors.initials: C
authors.lastname: Tu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Hsu
authors.forename: Hsu-Ping
authors.initials: HP
authors.lastname: Kuo
authors.forename: How-Wen
authors.initials: HW
authors.lastname: Ko
authors.forename: Jia
authors.initials: J
authors.lastname: Shen
authors.forename: Heng-Huan
authors.initials: HH
authors.lastname: Lee
authors.forename: Pei-Chih
authors.initials: PC
authors.lastname: Lee
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism* / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014443:Tyrosine; D066246:ErbB Receptors; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7