title: New insights into the functions of intersectin-1s.
abstract: Intersectin-1s (ITSN) is a ubiquitously expressed multifunctional protein known as a scaffold and regulator of the general endocytic machinery as well as a critical integrator of cellular signaling pathways. We showed recently that ITSN deficiency triggers a transforming growth factor β (TGFβ)/Alk5 signaling switch, from the canonical Smad 2/3 to the Erk1/2 MAPK pathway; moreover, endocytic impairment induced by ITSN deficiency enhances Alk5 ubiquitination and degradation and elicits TGFβ-paracrine effects mediated by circulating microparticles, leading to endothelial cell survival and increased proliferation. The studies expand our understanding of how ITSN facilitates cross-regulation of signaling pathways and provide insights into the involvement of ITSN deficiency in human disease.
authors.affiliation: Departments of Pharmacology and Critical Care Medicine; Rush University Medical Center ; Chicago, IL USA.
authors.forename: Sanda
authors.initials: S
authors.lastname: Predescu
authors.affiliation: Departments of Pharmacology and Critical Care Medicine; Rush University Medical Center ; Chicago, IL USA ; Department of Internal Medicine; Rush University Medical Center ; Chicago, IL USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bardita
authors.affiliation: Departments of Pharmacology and Critical Care Medicine; Rush University Medical Center ; Chicago, IL USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Predescu
keywords: TGFβ; TGFβRI; circulating microparticles; endocytic deficiency; intersectin-1s