INVESTIGADORES
REY Osvaldo
artículos
Título:
Regulated nucleocytoplasmic transport of protein kinase D in response to G protein-coupled receptor activation.
Autor/es:
REY O, SINNETT-SMITH J, ZHUKOVA E, ROZENGURT E.
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 2001 p. 49228 - 49235
ISSN:
0021-9258
Resumen:
Protein kinase D (PKD)/protein kinase C mu is a serine/threonine
protein kinase activated by growth factors, antigen-receptor
engagement, and G protein-coupled receptor (GPCR) agonists via a
phosphorylation-dependent mechanism that requires protein kinase C
(PKC) activity. In order to investigate the dynamic mechanisms
associated with GPCR signaling, the intracellular distribution of PKD
was analyzed in live cells by imaging fluorescent protein-tagged PKD
and in fixed cells by immunocytochemistry. We found that PKD shuttled
between the cytoplasm and the nucleus in both fibroblasts and
epithelial cells. Cell stimulation with mitogenic GPCR agonists that
activate PKD induced a transient nuclear accumulation of PKD that was
prevented by inhibiting PKC activity. The nuclear import of PKD
requires its cys2 domain in conjunction with a nuclear import receptor,
while its nuclear export requires its pleckstrin homology domain and a
competent Crm1-dependent nuclear export pathway. This study thus
characterizes the regulated nuclear transport of a signaling molecule
in response to mitogenic GPCR agonists and positions PKD as a serine
kinase whose kinase activity and intracellular localization is
coordinated by PKC.