The structure and function of protein kinase C-related kinases (PRKs)

Abstract

The protein kinase C-related kinase (PRK) family of serine/threonine kinases, PRK1, PRK2 and PRK3, are effectors for the Rho family small G proteins. An array of studies have linked these kinases to multiple signalling pathways and physiological roles, but while PRK1 is relatively well-characterized, the entire PRK family remains understudied. Here, we provide a holistic overview of the structure and function of PRKs and describe the molecular events that govern activation and autoregulation of catalytic activity, including phosphorylation, protein interactions and lipid binding. We begin with a structural description of the regulatory and catalytic domains, which facilitates the understanding of their regulation in molecular detail. We then examine their diverse physiological roles in cytoskeletal reorganization, cell adhesion, chromatin remodelling, androgen receptor signalling, cell cycle regulation, the immune response, glucose metabolism and development, highlighting isoform redundancy but also isoform specificity. Finally, we consider the involvement of PRKs in pathologies, including cancer, heart disease and bacterial infections. The abundance of PRK-driven pathologies suggests that these enzymes will be good therapeutic targets and we briefly report some of the progress to date.

Phosphorylation‐mediated PI3K‐Art signalling pathway as a therapeutic mechanism in the hydrogen‐induced alleviation of brain injury in septic mice

“…PKN may inhibit insulin signalling by directly interacting with PDK1 and Akt 29 . A previous study showed that PKN2 contributes to cell adhesion‐mediated activation of Akt 30 . Moreover, phosphoproteomics analysis of PKN2−/− mouse embryonic fibroblasts revealed that Akt pathway activity is increased in these cells 31 .…”

“… 29 A previous study showed that PKN2 contributes to cell adhesion‐mediated activation of Akt. 30 Moreover, phosphoproteomics analysis of PKN2−/− mouse embryonic fibroblasts revealed that Akt pathway activity is increased in these cells. 31 Furthermore, PKN2 knockdown impairs insulin‐responsive glucose metabolism and unexpectedly activates 5′‐adenosine monophosphate‐activated protein kinase, exerting downstream effects on lipid and protein metabolism.…”

Integrative analysis of genome and transcriptome reveal the genetic basis of high temperature tolerance in pleurotus giganteus (Berk. Karun & Hyde)

“…PKs also play roles in the immune response and nervous system function [ 60 ]. Among the protein kinases,, serine/threonine-protein kinases (STPKs) are the most extensively studied and include cyclin-dependent kinase (CDK), mitogen-activated protein kinase (MAPK), DNA-dependent protein kinase, natto kinase, and protein kinase C [ 61 ]. In our study, many genes encoding STPK were significantly regulated in P .…”

The Influence of Different γ-Irradiation Patterns on Factors that May Affect Cell Cycle Progression in Male Rats

“…These processes include cytoskeletal regulation, cell adhesion, apoptosis, regulation of meiotic maturation and signaling to the cell nucleus, and tumorigenesis. 14 …”

“…These processes include cytoskeletal regulation, cell adhesion, apoptosis, regulation of meiotic maturation and signaling to the cell nucleus, and tumorigenesis. 14 Another factor that may affect cell cycle progression and is affected by ionizing irradiation is transforming growth factorβ (TGF-β) which regulates a wide range of biological processes, including cell growth, differentiation, apoptosis, motility, immune regulation, cell invasion, and cell cycle regulation by blocking progress through the G1 phase. 15 On the other hand, the effect of TGF-β is dependent on the physiological environment.…”