title: Src tyrosyl phosphorylates cortactin in response to prolactin.
abstract: The hormone/cytokine prolactin (PRL) is implicated in breast cancer cell invasion and metastasis. PRL-induced pathways are mediated by two non-receptor tyrosine kinases, JAK2 and Src. We previously demonstrated that prolactin stimulates invasion of breast cancer cells TMX2-28 through JAK2 and its target serine/threonine kinase PAK1. We hypothesize herein that the actin-binding protein cortactin, a protein involved in invadopodia formation and cell invasion, is activated by PRL. We demonstrate that TMX2-28 cells are more invasive than T47D breast cancer cells in response to PRL. We determine that cortactin is tyrosyl phosphorylated in response to PRL in a time and dose-dependent manner in TMX2-28 cells, but not in T47D cells. Furthermore, we show that PRL mediates cortactin tyrosyl phosphorylation via Src, but not JAK2. Finally, we demonstrate that maximal PRL-mediated TMX2-28 cell invasion requires both Src and JAK2 kinase activity, while T47D cell invasion is JAK2- but not Src-dependent. Thus PRL may induce cell invasion via two pathways: through a JAK2/PAK1 mediated pathway that we have previously demonstrated, and Src-dependent activation and tyrosyl phosphorylation of cortactin.
authors.affiliation: The Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, Toledo, OH, 43606-3390, USA. Electronic address: alan.hammer@utoledo.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Hammer
authors.affiliation: The Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, Toledo, OH, 43606-3390, USA. Electronic address: sdlaghate@gmail.com.
authors.forename: Sneha
authors.initials: S
authors.lastname: Laghate
authors.affiliation: The Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, Toledo, OH, 43606-3390, USA. Electronic address: mdiakon@utnet.utoledo.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Diakonova
mesh_terms: D051356:Cortactin / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D011388:Prolactin / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D051356:Cortactin; D014443:Tyrosine; D011388:Prolactin; D019061:src-Family Kinases
keywords: Cell invasion; Cortactin; JAK2 kinase; Prolactin; Src kinase; Tyrosine kinase