PKD

Protein kinases are of utmost importance in maintaining a battery of cellular activities and the human genome encodes over 500 protein kinase genes which constitute about 2% of all human genes, collectively named as the human kinome. The protein kinase D (PKD) family of serine/threonine kinases falls in to the Ca++/Calmodulin-dependent protein kinases (CaMKs) superfamily and consists of three isoforms in mammals, notably, PKD1, PKD2 and PKD3. PKD1 was the first member identified in human and mouse, although initially it was categorized as a member of the protein kinase C (PKC) family and named PKCμ. It was later reclassified in to CaMK family based on sequence homology in the catalytic domain. PKD3 and PKD2, two additional PKD isoforms, were discovered thereafter.
 In a canonical pathway, various stimuli including hormones, phorbol esters, growth factors, cellular stress converge to the activation of PKDs through diacylglycerol (DAG) and classical or novel protein kinase C (c/nPKC) via active phospholipase C (PLC) β and γ. Activated PKD resides in diverse subcellular locations such as cytosol, Golgi apparatus, nucleus, mitochondria to regulate a plethora of cellular functions, especially those related to malignant transformation including cell proliferation, growth, migration/invasion, apoptosis, epidermal-to-mesenchymal transition (EMT).