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K153R polymorphism in myostatin gene increases the rate of promyostatin activation by furin
Author(s) -
Szláma György,
Trexler Mária,
Buday László,
Patthy László
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.12.011
Subject(s) - furin , myostatin , polymorphism (computer science) , biology , mutant , gene , genetics , skeletal muscle , allele , endocrinology , medicine , biochemistry , enzyme
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.