PRKD1

PRKD1 Full Name

protein kinase D1

PRKD1 Introduction

PRKD1, located on chromosome 14q11, encodes protein kinase D1, the founding member of the serine/threonine protein kinase D family. PRKD1 contains two N-terminal cysteine-rich C1 domains that bind diacylglycerol (DAG), a central pleckstrin homology domain, and a C-terminal catalytic domain related to calcium/calmodulin-dependent kinases. Activation occurs downstream of novel PKC isoforms in response to DAG and phorbol esters, after which PRKD1 translocates from the cytosol to the trans-Golgi network, nucleus, or mitochondria. It is widely expressed and integrates signals governing Golgi integrity, vesicle trafficking, cell migration, proliferation, survival, and cytoskeletal remodeling in multiple tissues.

Figure 1. A diagram illustrating the conserved structural domains and major phosphorylation sites in human protein kinase D (PKD) isoforms. (Source: Zhang X, et al. 2021)

Mechanistically, PRKD1 maintains Golgi membrane integrity by regulating fission of transport carriers destined for the plasma membrane and by phosphorylating lipid-handling substrates such as CERT and OSBP. In epithelial cells it suppresses epithelial-to-mesenchymal transition by phosphorylating Snail and modulating E-cadherin/β-catenin signaling, while in endothelial cells it controls VEGF-driven angiogenesis and barrier function through class IIa HDAC phosphorylation and nuclear export. Under oxidative stress, PRKD1 is activated via SRC-ABL1 to drive NF-κB survival signaling, and it also modulates the cofilin–SSH1L–cortactin pathway that fine-tunes actin-driven motility and invasion.

Disease associations of PRKD1 span both germline and somatic disorders. De novo heterozygous mutations cause a syndromic condition combining telangiectasia, ectodermal dysplasia, brachydactyly, and congenital heart defects, and additional PRKD1 variants—both dominant and recessive—have been linked to isolated congenital heart disease including pulmonary stenosis, truncus arteriosus, and atrial septal defect. Somatic PRKD1 hotspot mutations at p.Glu710Asp act as oncogenic drivers in over 70% of polymorphous low-grade adenocarcinomas of the salivary glands, while PRKD1 downregulation through promoter hypermethylation contributes to invasion and metastasis in breast, prostate, and colorectal cancers.

Alternate Names for PRKD1

PRKD1; protein kinase D1; PKD; PKCM; PRKCM; PKC-MU; serine/threonine-protein kinase D1; nPKC-D1; nPKC-mu; protein kinase D; protein kinase C, mu; protein kinase C mu type;

• 1. Alter S, et al. Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly syndrome is caused by de novo mutations in protein kinase D1. J Med Genet. 2021 Jun;58(6):415-421.
  2. Zhang X, et al. Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases. Biomolecules. 2021 Mar 23;11(3):483.