Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II

Hannah J. Durrington, Paul D. Upton, Simon Hoer, Jessica Boname, Benjamin J. Dunmore, Jun Yang, Trina K. Crilley, Lynn M. Butler, David J. Blackbourn, Gerard B. Nash, Paul J. Lehner, Nicholas W. Morrell

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)


Bone morphogenetic proteins (BMPs) are critically involved in early development and cell differentiation. In humans, dysfunction of the bone morphogenetic protein type II receptor (BMPR-II) is associated with pulmonary arterial hypertension (PAH) and neoplasia. The ability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma and primary effusion lymphoma, to down-regulate cell surface receptor expression is well documented. Here we show that KSHV infection reduces cell surface BMPR-II. We propose that this occurs through the expression of the viral lytic gene, K5, a ubiquitin E3 ligase. Ectopic expression of K5 leads to BMPR-II ubiquitination and lysosomal degradation with a consequent decrease in BMP signaling. The down-regulation by K5 is dependent on both its RING domain and a membrane-proximal lysine in the cytoplasmic domain of BMPR-II. We demonstrate that expression of BMPR-II protein is constitutively regulated by lysosomal degradation in vascular cells and provide preliminary evidence for the involvement of the mammalian E3 ligase, Itch, in the constitutive degradation of BMPR-II. Disruption of BMP signaling may therefore play a role in the pathobiology of diseases caused by KSHV infection, as well as KSHV-associated tumorigenesis and vascular disease.

Original languageEnglish
Pages (from-to)37641-37649
Number of pages9
JournalJournal of Biological Chemistry
Issue number48
Publication statusPublished - 26 Nov 2010


Dive into the research topics of 'Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II'. Together they form a unique fingerprint.

Cite this