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Identification of the structural determinant responsible for the phosphorylation of G‐protein activated potassium channel 1 by cAMP‐dependent protein kinase
Author(s) -
Müllner Carmen,
Steinecker Bibiane,
Gorischek Astrid,
Schreibmayer Wolfgang
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07325.x
Subject(s) - protein kinase a , phosphorylation , protein phosphorylation , map2k7 , protein subunit , protein kinase c , mitogen activated protein kinase kinase , g protein coupled inwardly rectifying potassium channel , cgmp dependent protein kinase , serine , biochemistry , biology , xenopus , phosphorylation cascade , kinase , c raf , microbiology and biotechnology , cyclin dependent kinase 2 , chemistry , signal transduction , g protein , gene
Besides being activated by G‐protein β/γ subunits, G‐protein activated potassium channels (GIRKs) are regulated by cAMP‐dependent protein kinase. Back‐phosphorylation experiments have revealed that the GIRK1 subunit is phosphorylated in vivo upon protein kinase A activation in Xenopus oocytes, whereas phosphorylation was eliminated when protein kinase A was blocked. In vitro phosphorylation experiments using truncated versions of GIRK1 revealed that the structural determinant is located within the distant, unique cytosolic C‐terminus of GIRK1. Serine 385, serine 401 and threonine 407 were identified to be responsible for the incorporation of radioactive 32 P into the protein. Furthermore, the functional effects of cAMP injections into oocytes on currents produced by GIRK1 homooligomers were significantly reduced when these three amino acids were mutated. The data obtained in the present study provide information about the structural determinants that are responsible for protein kinase A phosphorylation and the regulation of GIRK channels. Structured digital abstract• MINT‐7260296 , MINT‐7260317 , MINT‐7260333 , MINT‐7260347 , MINT‐7260361 , MINT‐7260270 : PKA‐cs (uniprotkb: P00517 ) phosphorylates ( MI:0217 ) Girk1 (uniprotkb: P63251 ) by protein kinase assay ( MI:0424 )