Study On The Role Of MS9 In Regulating Interaction Between EGFR And STAT3

The single transmembrane protein MS9 previously cloned in our lab is a molecular function yet unknown protein with a molecular weight of about 40 KDa.It includes an extracellular domain,a transmembrane domain and an intracellular domain.Membrane proteins have a variety of biological functions and can transfer information between extracellular environment and cellular lipoproteins.They play key roles in development of many human diseases including cancer,so that most of drugs target membrane proteins.Studies have found that membrane proteins can be used as various biological markers,and are mostly related to inter-cell signal transduction,immune diseases and the occurrence and development of tumors.Hence,it is important to study the relationship between membrane proteins and development of human diseases including tumor related signaling pathways.EGFR and STAT3 are frequently overexpressed in a variety of tumors.It is well known that EGFR may interact and phosphorylate STAT3 in response to binding of ligand such as EGF.Constitutive phosphorylation of STAT3 promotes the growth of cancer cells.Our previous study found that MS9 can interact with EGFR.We studied the regulation of MS9 on the interaction between EGFR and STAT3,and how it affects the EGFR/STAT3 signaling pathway.We found that co-expression of MS9 significantly inhibited the binding of EGFR to STAT3 and the phosphorylation of STAT3 by EGFR in cells.In addition,in vitro GST pull down assay and phosphorylation assay further confirmed that MS9 competitively interacts with EGFR to block the interaction between EGFR and STAT3 and inhibits the phosphorylation of STAT3 mediated by EGFR,indicating a negative regulation of EGFR/STAT3 signaling pathway by MS9.