INVESTIGADORES
REY Osvaldo
artículos
Título:
The nuclear import of protein kinase D3 requires its catalytic activity.
Autor/es:
REY O, PAPAZYAN R, WALDRON RT, YOUNG SH, LIPPINCOTT-SCHWARTZ J, JACAMO R, ROZENGURT E.
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 2006 p. 5149 - 5157
ISSN:
0021-9258
Resumen:
The protein kinase D (PKD) family consists of three serine/threonine
protein kinases termed PKD, PKD2, and PKD3, which are similar in
overall structure and primary amino acid sequence. However, each
isozyme displays a distinctive intracellular localization. Taking
advantage of the structural homology and opposite nuclear localization
of PKD2 and PKD3, we generated an extensive set of chimeric proteins
between both isozymes to determine which PKD3 domain(s) mediates its
nuclear localization. We found that the C-terminal region of PKD3,
which contains its catalytic domain, is necessary but not sufficient
for its nuclear localization. Real time imaging of a photoactivatable
green fluorescent protein fused to PKD3 revealed that point mutations
that render PKD3 catalytically inactive completely prevented its
nuclear import despite its interaction with importin alpha and beta. We
also found that activation loop phosphorylation of PKD3 did not require
its nuclear localization, and it was not sufficient to promote the
nuclear import of PKD3. These results identify a novel function for the
kinase activity of PKD3 in promoting its nuclear entry and suggest that
the catalytic activity of PKD3 may regulate its nuclear import through
autophosphorylation and/or interaction with another protein(s).