Tyrosine Phosphorylation of Grb2: Role in Prolactin/Epidermal Growth Factor Cross Talk in Mammary Epithelial Cell Growth and Differentiation

• DOI: 10.1128/mcb.00034-09
• Publication Date: 2009-03-10T01:08:52Z
• Authors: Eric Haines; Parham Minoo; Zhenqian Feng; Nazila Resalatpanah; Xin-Min Nie; Manuela Campiglio; Laura Alvarez; Eftihia Cocolakis; Mohammed Ridha; Mauricio Di Fulvio; Julian Gomez-Camb...; Jean-Jacques Lebrun; Suhad Ali
• Keywords: GRB2

Characterizing mechanisms regulating mammary cell growth and differentiation is vital, as they may contribute to breast carcinogenesis. Here, we examine a cross talk mechanism(s) downstream of prolactin (PRL), primary hormone, epidermal factor (EGF), an important proliferative factor, in epithelial differentiation. Our data indicate that EGF exerts inhibitory effects on PRL-induced cellular by interfering with Stat5a-mediated gene expression independent the PRL-proximal signaling cascade. Additionally, our show PRL potent inhibitor EGF-induced proliferation. We identify tyrosine phosphorylation receptor-bound protein 2 (Grb2) critical mechanism which antagonizes proliferation attenuating activation Ras/mitogen-activated kinase (MAPK) pathway. Together, results define novel negative cross-regulation between involving Jak2/Stat5a Ras/MAPK pathways through Grb2.