Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 293, Issue 37, Pages 14407-14416Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA118.003787
Keywords
protein kinase D (PKD); Rho (Rho GTPase); deleted in liver cancer 1 (DLC1); secretion; kinetics; model selection; profile likelihood; trans-Golgi network; kinetic modeling
Categories
Funding
- Heisenberg program of the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG)) [OL239/8]
- DFG within the Cluster of Excellence in Simulation Technology at the University of Stuttgart [EXC 310/2]
Ask authors/readers for more resources
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 GTPase-activating 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 Rho-Rho-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 Rho-ROCK signaling. We propose that PKD senses cytoskeletal changes downstream of DLC1 to coordinate Rho signaling with Golgi secretory function.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available