Abstract
Protein kinase D isoenzymes (PKDs, Prkds) are serine threonine kinases that belong to the CAMK superfamily. PKD1 is expressed in endothelial cells and is a major mediator of biological responses downstream of the VEGFRs that are relevant for angiogenesis such as endothelial cell migration, proliferation and tubulogenesis in vitro. PKDs also play a critical role in tumor development and progression, including tumor angiogenesis. However, given the plethora of signaling modules that drive angiogenesis, the precise role of PKD1 in both physiological and tumor angiogenesis in vivo has not been worked out so far. This study aimed at dissecting the contribution of PKD1 to physiological blood vessel formation, PKD1 was found to be widely expressed during zebrafish development. As far as physiological angiogenesis was concerned, morpholino-based silencing of PKD1 expression moderately reduced the formation of the intersomitic vessels and the dorsal longitudinal anastomotic vessel in tg(fli1:EGFP) zebrafish. In addition, silencing of PKD1 resulted in reduced formation of the parachordal lymphangioblasts that serves as a precursor for the developing thoracic duct. Interestingly, tumor angiogenesis was completely abolished in PKD1 morphants using the zebrafish/tumor xenograft angiogenesis assay. Our data in zebrafish demonstrate that PKD1 contributes to the regulation of physiological angiogenesis and lymphangiogenesis during zebrafish development and is essential for tumor angiogenesis.
Highlights
The protein kinase D (PKD, Prkd) family of serine threonine kinases belongs to the calcium/calmodulin-dependent protein kinase superfamily [1] and comprises three isoforms [2]
Green fluorescent nuclei of endothelial cells from the trunk vasculature - including the dorsal aorta (DA), the posterior cardinal vein (CV), the intersomitic vessels (ISV) and the dorsal longitudinal anastomotic vessel (DLAV) - colocalized with the cytoplasmatic signal of Protein Kinase D1 (PKD1) antibody staining
PKD1 activity is required for the biological responses downstream of the VEGFR tyrosine kinase in endothelial cells and important for migration, proliferation and tubulogenesis, the relevant biological processes leading to angiogenesis [10,15,38]
Summary
The protein kinase D (PKD, Prkd) family of serine threonine kinases belongs to the calcium/calmodulin-dependent protein kinase superfamily [1] and comprises three isoforms [2]. The N-terminal domain, and the zinc finger motifs in particular, are important in regulating PKD subcellular localization [3]. PKDs are activated by various stimuli, including phorbol esters, G-protein-coupled receptors and reactive oxygen species [4]. PKDs act as prominent downstream targets of PKCs, including novel PKCg and PKCe [5,6]. PKCs directly activate PKDs via phosphorylation at two critical serine residues within the activation loop of the catalytic domain [7]. PKDs can be activated by direct binding of diacylglycerol (DAG) to the C1a domain [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
