Opposing mitogenic and anti-mitogenic actions of parathyroid hormone-related protein in vascular smooth muscle cells: A critical role for nuclear targeting

• DOI: 10.1073/pnas.94.25.13630
• Publication Date: 2002-07-26T14:35:50Z
• Authors: Thierry Massfelder; Pamela Dann; Terence L. Wu; Rupangi Vasavada; Jean-Jacques Helwig; Andrew F. Stewart
• Keywords: Intracrine; Parathyroid hormone-related protein

Parathyroid hormone-related protein (PTHrP) is a prohormone that posttranslationally processed to family of mature secretory forms, each which has its own cognate receptor(s) on the cell surface mediate actions PTHrP. In addition being secreted via classical pathway and interacting with receptors in paracrine/autocrine fashion, PTHrP appears be able enter nucleus directly following translation influence cellular events an "intracrine" fashion. this report, we demonstrate can targeted vascular smooth muscle cells, nuclear targeting associated striking increase mitogenesis, effect proliferation diametric opposite effects resulting from interaction regions sequence responsible for represent bipartite localization signal. This report describes activation cycle association any type. These findings have important implications normal physiology many tissues produce it, suggest gene delivery or modified variants may useful management atherosclerotic disease.