PRKD1: A Potential Drug Target and Biomarker for Proteolytic Enrichment-Induced Pain

Target Name: PRKD1

NCBI ID: G5587

PRKD1

PRKD1: A Potential Drug Target and Biomarker for Proteolytic Enrichment-Induced Pain

Abstract:

Proteolytic-induced pain is a persistent and debilitating condition that can be difficult to manage. PRKD1, a protein kinase C (PKC), is involved in the regulation of pain signaling pathways. In this article, we discuss the role of PRKD1 as a potential drug target and biomarker for proteolytic-induced pain. We review the current literature on PRKD1, including its role in pain signaling pathways, its potential as a drug target, and its potential as a biomarker for pain assessment.

Introduction:

Pain is a crucial signaling system that helps the body to maintain homeostasis and enables adaptive behaviors to respond to threats. The pain signaling pathway involves the production and release of pro-inflammatory cytokines and neuropeptides, which activate pain modalities such as nociception, inflammation, and neurogenic pain modalities.

Proteolytic-induced pain is a type of pain that is generated by the breakdown of extracellular matrix (ECM) components, such as collagen and casein, by enzymes called proteases. These proteases cause the release of pro-inflammatory cytokines and neuropeptides, leading to inflammation , pain, and functional changes in the affected region.

PRKD1: A Potential Drug Target

PRKD1 is a key protein kinase that is involved in the regulation of pain signaling pathways. It is a 21 kDa protein that is expressed in various tissues, including brain, heart, skeletal muscles, and intestine. PRKD1 is involved in the regulation of pain signaling. by modulating the activity of several downstream targets, including:

1. Pyruvate Kinase (PK): PRKD1 has been shown to phospho orylate PK, leading to its activation and subsequent activation of downstream targets, such as the cAMP-dependent protein kinase (PKA).
2. casein kinase (CaK): PRKD1 has been shown to phosphorylate CaK, leading to its activation and subsequent activation of downstream targets, such as the neurotransmitter-gated ion channel (Na+/K+-ATPase).
3. FAK: PRKD1 has been shown to phosphorylate FAK, leading to its activation and subsequent activation of downstream targets, such as the transcription factor (NF-kappa-B).

In addition to modulating the activity of these downstream targets, PRKD1 has also been shown to regulate the activity of several upstream targets, including the serine/thiolate enzyme, thioredoxin reductase (TXR), which is involved in the detoxification of oxidative stress damage to ECM components.

PRKD1 has also been shown to play a role in the regulation of pain modulatory neurotransmitters, such as calcitonin, oxytocin, and endogenous opioids.

PRKD1 as a Biomarker

PRKD1 has also been shown to be involved in the regulation of pain signaling pathways and its expression has been associated with the development and progression of pain conditions. For example, PRKD1 has been shown to be involved in the regulation of pain in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

In addition, PRKD1 has also been shown to be involved in the regulation of pain in inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease.

PRKD1 has also been shown to be involved in the regulation of pain in neurotraumatic diseases, such as post-traumatic stress disorder (PTSD) and chronic pain.

Conclusion:

In conclusion, PRKD1 is a protein kinase that is involved in the regulation of pain signaling pathways. It has been shown to play a role in the regulation of pain modulators, such as pro-inflammatory cytokines and neuropeptides, and in the regulation of pain signaling pathways. PRKD1 is also involved in the regulation of pain in various tissues and conditions, including pain signaling pathways

Protein Name: Protein Kinase D1

Functions: Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity)

The "PRKD1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about PRKD1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

More Common Targets