www.kjurology.org DOI:10.4111/kju.2010.51.8.511 Review Article Bone Morphogenetic Protein Signaling: Implications in Urology Jeongyun Jeong1, Dong Il Kang1,2, Geun Taek Lee1, Isaac Yi Kim1 1Department of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA, 2Department of Urology, Inje University College of Medicine, Busan, Korea The bone morphogenetic proteins (BMPs), as members of the transforming growth fac- tor-β (TGF-β) superfamily, not only control bone formation, but also regulate multiple key steps during embryonic development and differentiation. Furthermore, BMPs play critical roles in maintaining the homeostasis of the cardiovascular, pulmonary, re- productive, urogenital, and nervous systems in adult life. Like all members of the TGF-β superfamily, BMP signaling is mediated through a heteromeric complex of type I and type II transmembrane serine/threonine kinase receptors. The subsequent signal transduction cascade includes either the canonical Smad-dependent or non-canonical Smad-independent pathways. Reflecting the critical function of BMPs, BMP signaling is tightly regulated at multiple steps by various mechanisms including extracellular endogenous antagonists, neutralizing antibodies/extracellular soluble receptor do- mains, small molecule inhibitors, cytoplasmic inhibitory Smads, and transcriptional co-repressors. Recently, dorsomorphin, the first small molecule inhibitor of BMP sig- naling, was identified and suggested as a useful tool for dissecting the mechanisms of signaling pathways and for developing novel therapeutics for diverse human diseases that are related to the BMP signaling pathways. In this article, we discuss various mech- anisms involved in regulating BMP signaling pathways and their implications for urology. Key Words: Bone morphogenetic proteins; Dorsomorphin; Signal transduction; Trans- forming growth factors This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Article History: received 28 June, 2010 accepted 18 July, 2010 Corresponding Author: Isaac Yi Kim Section of Urologic Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, 195 Little Albany Street, #4560, New Brunswick, NJ 08901, USA TEL: +1-732-235-2043 FAX: +1-732-235-6596 E-mail: kimiy@umdnj.edu INTRODUCTION Bone morphogenetic proteins (BMPs) are pleiotropic cyto- kines and members of the transforming growth factor-β (TGF-β) superfamily that include TGF-βs, activins, and mullerian inhibitory substance (MIS) [1]. Originally, BMPs were isolated from bone extract and were named for their effect on cartilage formation and de novo bone for- mation [2]. During the last two decades, over 20 different BMPs have been identified in both vertebrates and in- vertebrates [3]. 　More recently, detailed studies have revealed that BMPs not only control bone formation but also regulate embry- onic development and differentiation [4-6]. Indeed, as with other members of the TGF-β superfamily, BMPs are im- portant for gastrulation, mesoderm induction, organo- Korean Journal of Urology Ⓒ The Korean Urological Association, 2010 genesis, proliferation, and apoptosis of multi-potent cells [7]. Besides the effect on embryonic development and dif- ferentiation, BMPs also play a critical role in homeostasis of the cardiovascular, pulmonary, reproductive, urogen- ital, and nervous systems in mature organisms [8]. Hence, BMPs have been linked to certain diseases such as primary pulmonary hypertension, fibrodysplasia ossificans pro- gressiva, and juvenile polyposis syndrome [9-11]. Further- more, recent reports in oncology revealed that BMPs are linked to carcinogenesis, including colorectal, ovarian, and lung cancers and melanoma [12-15]. Simultaneously, it has been reported that BMP-7 promotes brown adipoge- nesis. Specifically, Tseng et al reported that BMP-7 ini- tiates the commitment of mesenchymal progenitor cells to a brown adipocyte linage and promotes the differentiation of brown preadipocytes [16]. Brown adipose tissue, unlike 511 Korean J Urol 2010;51:511-517