title: Endothelial cell-specific molecule 2 (ECSM2) modulates actin remodeling and epidermal growth factor receptor signaling.
abstract: Endothelial cell-specific molecules (ECSMs) play a pivotal role in the pathogenesis of many angiogenesis-related diseases. Since its initial discovery, the exact function of human ECSM2 has not been defined. In this study, by database mining, we identified a number of hypothetical proteins across species exhibiting substantial sequence homology to the human ECSM2. We showed that ECSM2 is preferentially expressed in endothelial cells and blood vessels. Their characteristic structures and unique expression patterns suggest that ECSM2 is an evolutionarily conserved gene and may have important functions. We further explored the potential roles of human ECSM2 at the molecular and cellular level. Using a reconstitution mammalian cell system, we demonstrated that ECSM2 mainly resides at the cell membrane, is critically involved in cell-shape changes and actin cytoskeletal rearrangement, and suppresses tyrosine phosphorylation signaling. More importantly, we uncovered that ECSM2 can cross-talk with epidermal growth factor receptor (EGFR) to attenuate the EGF-induced cell migration, possibly via inhibiting the Shc-Ras-ERK (MAP kinase) pathway. Given the importance of growth factor and receptor tyrosine kinase-mediated signaling and cell migration in angiogenesis-related diseases, our findings regarding the inhibitory effects of ECSM2 on EGF-mediated signaling and cell motility may have important therapeutic implications.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, College of Life Science, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Fanxin
authors.initials: F
authors.lastname: Ma
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Hansuo
authors.initials: H
authors.lastname: Yang
authors.forename: Huaqin
authors.initials: H
authors.lastname: Sun
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Gan
authors.forename: James
authors.initials: J
authors.lastname: Balducci
authors.forename: Yu-quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D015027:Zebrafish
chemical_list: D000199:Actins; D051017:Apoptosis Regulatory Proteins; C531407:ECSCR protein, human; D008565:Membrane Proteins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors