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Regulation of Creatine Kinase Activity by Phosphorylation of Serine‐199 by AMP‐Activated Kinase
Author(s) -
Palmer Allyson K,
Fraga Dean,
Edmiston Paul L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1012.10
Subject(s) - phosphocreatine , phosphorylation , serine , creatine kinase , kinase , creatine , biochemistry , chemistry , protein kinase a , adenosine triphosphate , microbiology and biotechnology , biology , energy metabolism , endocrinology
Creatine kinase (CK) catalyzes the reversible phosphorylation of creatine by MgATP to form phosphocreatine and MgADP. An accessible reservoir of high energy phosphate in the form of phosphocreatine is useful in excitable tissues (i.e. brain, heart, or muscle) which require large energy fluxes. Thus, CK is important to energy homeostasis in cells. Previous work has suggested that AMP‐activated kinase may regulate the activity of CK by phosphorylation, presumably at a serine residue (Ponticos, et al. EMBO J . 17:1688.). To confirm this hypothesis, a set of serines in CK were changed to glutamate by site‐directed mutagenesis to assess if any of these residues were possible phosphorylation sites. Notably, the S199E variant of CK showed a 200‐fold reduction in the catalytic rate constant (phosphocreatine formation) compared to wild‐type suggesting that phosphorylation of S199 is likely involved in regulation of CK. The possible means by which phosphorylation alters the active site will be discussed. These results point to a higher degree of cellular control of ATP concentration by regulating the activity of CK. Such a regulatory mechanism may have implications on better understanding energy flux within a cell.