K153R polymorphism in myostatin gene increases the rate of promyostatin activation by furin.

Abstract

Recent studies demonstrated an association between the K153R polymorphism in the myostatin gene with extreme longevity, lower muscle strength and obesity but the molecular basis of these associations has not been clarified. Here, we show that the K153R mutation significantly increases the rate of proteolysis of promyostatin by furin, but has no effect on the activity of the latent complex or the cleavage of the latent complex by bone morphogenetic protein 1 (BMP-1). The increased rate of activation of K153R mutant promyostatin may explain why this polymorphism is associated with obesity, lower muscle strength and extension of lifespan.

• Authors: György Szláma, Mária Trexler, László Buday, László Patthy
• Journal: FEBS letters (FEBS Lett) Vol. 589 Issue 3 Pg. 295-301 (Jan 30 2015) ISSN: 1873-3468 [Electronic] England
• PMID: 25543063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• MSTN protein, human
• Myostatin
• Furin
• BMP1 protein, human
• Bone Morphogenetic Protein 1

Topics

• Aging (genetics, pathology)
• Bone Morphogenetic Protein 1 (metabolism)
• Furin (genetics, metabolism)
• HEK293 Cells
• Humans
• Longevity (genetics)
• Muscle Strength (genetics)
• Muscle, Skeletal (metabolism, pathology)
• Mutation
• Myostatin (biosynthesis, genetics)
• Obesity (genetics, pathology)
• Polymorphism, Single Nucleotide
• Protein Conformation