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

•The K153R mutation of promyostatin increases the rate of its activation by furin.•The K153R mutation does not affect activity of furin-activated myostatin.•The K153R mutation does not affect cleavage of latent myostatin by BMP-1.•Increased activation of K153R promyostatin may explain association wi...

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Bibliographic Details
Published in:FEBS letters 2015-01, Vol.589 (3), p.295-301
Main Authors: Szláma, György, Trexler, Mária, Buday, László, Patthy, László
Format: Article
Language:English
Subjects:
Aging
Aging - genetics
Aging - pathology
BMP
bone morphogenetic protein
Bone Morphogenetic Protein 1 - metabolism
bovine serum albumin
BSA
FBS
fetal bovine serum
Furin - genetics
Furin - metabolism
HEK293 Cells
Humans
Lifespan
Longevity
Longevity - genetics
MSTN
Muscle strength
Muscle Strength - genetics
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Mutation
Myostatin
Myostatin - biosynthesis
Myostatin - genetics
myostatin gene
Obesity
Obesity - genetics
Obesity - pathology
phenylmethylsulfonyl fluoride
PMSF
Polymorphism, Single Nucleotide
Protein Conformation
TGF
transforming growth factor
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Summary:•The K153R mutation of promyostatin increases the rate of its activation by furin.•The K153R mutation does not affect activity of furin-activated myostatin.•The K153R mutation does not affect cleavage of latent myostatin by BMP-1.•Increased activation of K153R promyostatin may explain association with longevity. 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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2014.12.011