Premium
Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation
Author(s) -
Cobbaut Mathias,
Derua Rita,
Parker Peter J.,
Waelkens Etienne,
Janssens Veerle,
Van Lint Johan
Publication year - 2018
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 - 10.1002/1873-3468.13171
Subject(s) - autophosphorylation , phosphorylation , kinase , microbiology and biotechnology , in vitro , chemistry , biochemistry , pkd1 , protein kinase a , biology , genetics , polycystic kidney disease , kidney
The protein kinase D ( PKD ) family is regulated through multi‐site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser‐742 (and Ser‐738 in vitro ) in the activation loop and Ser‐910 in the C‐tail ( hPKD 1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P + 1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD 1) in the catalytic loop as of utmost importance. In cells, PKD Tyr autophosphorylation is suppressed through the association of an inhibitory factor. Our findings provide important novel insights into PKD (auto)regulation.