Many newly synthesized cellular proteins pass through the Golgi complex
from where secretory transport carriers sort them to the plasma membrane
and the extracellular environment. The formation of these secretory
carriers at the trans-Golgi network is promoted by the protein kinase
D (PKD) family of serine/threonine kinases. Here, using mathematical
modeling and experimental validation of the PKD activation and substrate
phosphorylation kinetics, we reveal that the expression level of
the PKD substrate deleted in liver cancer 1 (DLC1), a Rho GTPaseactivating
protein that is inhibited by PKD-mediated phosphorylation, determines
PKD activity at the Golgi membranes. RNAi-mediated depletion of DLC1
reduced PKD activity in a RhoRho-associated protein kinase (ROCK)dependent
manner, impaired the exocytosis of the cargo protein horseradish
peroxidase, and was associated with the accumulation of the small
GTPase RAB6 on Golgi membranes, indicating a protein-trafficking
defect. In summary, our findings reveal that DLC1 maintains basal
activation of PKD at the Golgi and Golgi secretory activity, in part
by down-regulating RhoROCK signaling. We propose that PKD senses
cytoskeletal changes downstream of DLC1 to coordinate Rho signaling
with Golgi secretory function.
%0 Journal Article
%1 ist:jensch2018
%A Jensch, Antje
%A Frey, Yannick
%A Bitschar, Katharina
%A Weber, Patrick
%A Schmid, Simone
%A Hausser, Angelika
%A Olayioye, Monilola A.
%A Radde, Nicole E.
%D 2018
%J J. Biol. Chem.
%K imported
%N 37
%P 14407-14416
%R 10.1074/jbc.RA118.003787
%T The tumor suppressor protein DLC1 maintains protein kinase D activity and Golgi secretory function
%U http://www.jbc.org/content/293/37/14407.abstract
%V 293
%X Many newly synthesized cellular proteins pass through the Golgi complex
from where secretory transport carriers sort them to the plasma membrane
and the extracellular environment. The formation of these secretory
carriers at the trans-Golgi network is promoted by the protein kinase
D (PKD) family of serine/threonine kinases. Here, using mathematical
modeling and experimental validation of the PKD activation and substrate
phosphorylation kinetics, we reveal that the expression level of
the PKD substrate deleted in liver cancer 1 (DLC1), a Rho GTPaseactivating
protein that is inhibited by PKD-mediated phosphorylation, determines
PKD activity at the Golgi membranes. RNAi-mediated depletion of DLC1
reduced PKD activity in a RhoRho-associated protein kinase (ROCK)dependent
manner, impaired the exocytosis of the cargo protein horseradish
peroxidase, and was associated with the accumulation of the small
GTPase RAB6 on Golgi membranes, indicating a protein-trafficking
defect. In summary, our findings reveal that DLC1 maintains basal
activation of PKD at the Golgi and Golgi secretory activity, in part
by down-regulating RhoROCK signaling. We propose that PKD senses
cytoskeletal changes downstream of DLC1 to coordinate Rho signaling
with Golgi secretory function.
@article{ist:jensch2018,
abstract = {Many newly synthesized cellular proteins pass through the Golgi complex
from where secretory transport carriers sort them to the plasma membrane
and the extracellular environment. The formation of these secretory
carriers at the trans-Golgi network is promoted by the protein kinase
D (PKD) family of serine/threonine kinases. Here, using mathematical
modeling and experimental validation of the PKD activation and substrate
phosphorylation kinetics, we reveal that the expression level of
the PKD substrate deleted in liver cancer 1 (DLC1), a Rho GTPaseactivating
protein that is inhibited by PKD-mediated phosphorylation, determines
PKD activity at the Golgi membranes. RNAi-mediated depletion of DLC1
reduced PKD activity in a RhoRho-associated protein kinase (ROCK)dependent
manner, impaired the exocytosis of the cargo protein horseradish
peroxidase, and was associated with the accumulation of the small
GTPase RAB6 on Golgi membranes, indicating a protein-trafficking
defect. In summary, our findings reveal that DLC1 maintains basal
activation of PKD at the Golgi and Golgi secretory activity, in part
by down-regulating RhoROCK signaling. We propose that PKD senses
cytoskeletal changes downstream of DLC1 to coordinate Rho signaling
with Golgi secretory function.},
added-at = {2021-05-18T15:30:24.000+0200},
author = {Jensch, Antje and Frey, Yannick and Bitschar, Katharina and Weber, Patrick and Schmid, Simone and Hausser, Angelika and Olayioye, Monilola A. and Radde, Nicole E.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/20ed78cf5ff45e2542e648b5a57035cf8/ist_bib},
doi = {10.1074/jbc.RA118.003787},
eprint = {http://www.jbc.org/content/293/37/14407.full.pdf+html},
interhash = {5be5d3ed6b8348c67cc7d74dc513751c},
intrahash = {0ed78cf5ff45e2542e648b5a57035cf8},
journal = {J. Biol. Chem.},
keywords = {imported},
number = 37,
pages = {14407-14416},
timestamp = {2021-05-18T13:32:10.000+0200},
title = {The tumor suppressor protein DLC1 maintains protein kinase D activity and Golgi secretory function},
url = {http://www.jbc.org/content/293/37/14407.abstract},
volume = 293,
year = 2018
}