VRK (Vaccinia-Related Kinases) are three proteins in human kinases. These proteins, mainly VRK1 and VRK2, have been studied in the context of their substrates and interacting proteins to identify and characterize their signaling pathways and their effects on other signaling pathways. VRK1 is a nuclear kinase that specifically phosphorylates p53, c-Jun, ATF2, CREB, BAF, and histone H3. VRK1 is an early response gene and is involved in the regulation of cell cycle processes. VRK1 is activated in response to DNA damage to phosphorylate p53, which is stabilized and activated. This active p53 induces the down-regulation mechanism of VRK1 and can reverse the effect of p53 induction. Nuclear activity VRK1 is regulated by interaction with Ran small GTPase. In addition, VRK1 is a downstream component of the signaling pathway, MEK-Plk3, which induces Golgi fragmentation during mitosis.
VRK1
The serine/threonine protein kinase VRK1 is an enzyme encoded by the VRK1 gene in humans, which encodes a member of the vaccinia-related kinase (VRK) family of serine / threonine protein kinases. The gene is widely expressed in human tissues and increased in actively dividing cells such as testes, thymus, fetal liver, and cancerous tissues. Its protein is localized in the nucleus and has been shown to promote the stability and nuclear accumulation of transcriptionally active p53 molecules, and phosphorylate Thr18 of p53 in vitro and reduce p53 ubiquitination. Therefore, this gene may regulate cell proliferation. The protein also phosphorylates histones, casein, and the transcription factor ATF2 (activating transcription factor 2) and C-jun.
VRK2
The serine/threonine protein kinase VRK2 is an enzyme encoded by the VRK2 gene in humans, which encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The gene is widely expressed in human tissues and increased in actively dividing cells such as testes, white blood cells, fetal liver, and cancerous tissues. Its protein is localized in the endoplasmic reticulum and has been shown to phosphorylate casein and undergo autophosphorylation.
Biological role of VRK protein
The biological information on these three VRK proteins is very limited, and most of the information is obtained by studying human proteins in two main directions. One of them hints at the characteristics of the signaling pathways involved in VRK proteins through substrate identification or through interaction with other proteins. The other is to target their effects on certain biological responses, such as hypoxia, interleukin 1β or DNA damage. In both cases, as these proteins gain more relevance in the context of tumor biology, the information is expected to expand and begin to attract more attention. In the case of VRK1, some of its targets have been identified, including several transcription factors, which can serve as a starting point for characterizing the VRK pathway itself or their VRK pathway interaction with other pathways.
VRK2 down-regulates JNK-mediated response to hypoxia or interleukin 1β
In many biological processes induced by growth factors, stress responses send signals that activate gene expression. These signals are guided by a protein complex of mitogen-associated protein kinase (MAPK), which is activated by two additional kinases, MAPKK and MAPKKK, ordered in sequential steps. MAP kinases represent the core of multiple signaling pathways that respond to a variety of stimuli from growth factors to stress responses. This response suggests multiple biological effects, such as proliferation, apoptosis, growth arrest, and aging. These three kinases are usually anchored to scaffold proteins. The most famous are JIP1 (which has four members) and KSR1. However, there are other little-known stents. Scaffold protein levels and subcellular localization are critical to determining the distribution of signals between different signaling pathways, and this asymmetry in signal distribution can determine the ultimate biological effect. These complexes may interact to further regulate other proteins that activate or inhibit signaling; there are two VRK2 isoforms in these proteins. Therefore, signal specificity may be determined by the interaction between the components of the core signaling pathway and other proteins, most of which have not been identified, but this is an emerging field. Among these proteins, VRK2A and VRK3 have been shown to interact and regulate MAP kinase signaling in response to different types of stimuli.
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