NK-1R Antibody [A17A4] | Primary Antibodies

Application: Reactivity: Mouse, Human, Rat

Usage Information

Dilution
IHC1:2000 FCM1:500

Application
IHC, FCM

Reactivity
Mouse, Human, Rat

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
46 kDa

Datasheet & SDS

Biological Description

Specificity
NK-1R Antibody [A17A4] detects endogenous levels of total NK-1R protein.

Clone
A17A4

Synonym(s)
Tac1r, Substance-P receptor, SPR, NK-1 receptor, Tachykinin receptor 1, NK-1R

Background
Neurokinin‑1 receptor (NK‑1R; TACR1) is the prototypic tachykinin G protein‑coupled receptor that displays highest affinity for substance P and lower affinity for neurokinin A, neurokinin B, hemokinin‑1 and endokinins, integrating neuropeptidergic, vascular, and immune signals across nervous, cardiovascular, gastrointestinal, and hematopoietic systems. NK‑1R is a class A seven‑transmembrane GPCR with three extracellular and three intracellular loops, an N‑terminal extracellular domain containing N‑linked glycosylation sites that stabilize the receptor at the plasma membrane, and a cytoplasmic C‑terminal tail enriched in serine/threonine residues that governs G‑protein coupling, β‑arrestin recruitment, desensitization, and internalization; alternative splicing generates a full‑length 407‑residue isoform and a truncated 311‑residue isoform lacking most of the C‑terminus with markedly different signaling properties. Substance P binding to full‑length NK‑1R preferentially engages Gq/11 proteins to activate phospholipase Cβ, driving hydrolysis of phosphatidylinositol 4,5‑bisphosphate into inositol 1,4,5‑trisphosphate and diacylglycerol, release of intracellular Ca²⁺, and protein kinase C activation; parallel coupling to Gs stimulates adenylyl cyclase, elevates cAMP, activates protein kinase A, and modulates CREB‑dependent transcription, while G12/13 linkage activates Rho/ROCK to control actomyosin contractility and membrane blebbing during migration. Downstream, NK‑1R signaling activates Ras/Raf/MEK/ERK and p38 MAPK cascades, PI3K–Akt pathways, and NF‑κB, leading to induction of immediate‑early genes (c‑fos, c‑myc), cell‑cycle regulators, and a spectrum of pro‑inflammatory mediators including IL‑1, IL‑6, IL‑8, TNF‑α, MIP‑1β and IFN‑γ that link neurogenic input to innate and adaptive immune responses. Full‑length NK‑1R efficiently couples to calcium mobilization, rapid and sustained ERK activation, NF‑κB activation, IL‑8 transcription, and PKCδ phosphorylation, whereas the truncated isoform displays roughly ten‑fold lower affinity for substance P, fails to mobilize calcium, does not activate NF‑κB or IL‑8, and shows delayed, attenuated ERK phosphorylation, reflecting loss of C‑terminal phosphorylation sites required for G protein‑coupled receptor kinase interaction and β‑arrestin‑scaffolded signalosomes. NK‑1R is widely expressed on sensory and autonomic neurons, astrocytes, microglia, and vascular endothelium where it mediates nociceptive transmission, neurogenic inflammation, vasodilation, and emesis, and is enriched in brainstem regions such as nucleus tractus solitarius and area postrema that control vomiting, providing the anatomical basis for the clinical efficacy of high‑affinity NK‑1R antagonists aprepitant and fosaprepitant in chemotherapy‑induced nausea and vomiting. The receptor is also expressed on monocytes, macrophages, dendritic cells, T and B lymphocytes, NK cells, and bone marrow progenitors, where substance P–NK‑1R signaling enhances chemotaxis, cytokine production, respiratory burst, and survival, thereby amplifying antibacterial, antiviral, and antifungal responses while contributing to chronic inflammatory pathology in disorders such as inflammatory bowel disease, arthritis, and airway hyper‑responsiveness. In the immune context, NK‑1R signaling in monocyte–macrophages and lymphocytes augments NF‑κB‑driven cytokine output and modulates expression of chemokine receptors including CCR5, with NK‑1R antagonists reducing HIV entry and replication in mononuclear phagocytes and peripheral blood mononuclear cells through down‑regulation of CCR5 and disruption of an SP‑driven feed‑forward loop. NK‑1R internalization, recycling, and signaling duration are tightly shaped by C‑terminal phosphorylation and β‑arrestin binding: full‑length NK‑1R forms β‑arrestin/Src/ERK complexes that can retain active ERK in the cytoplasm or enable nuclear translocation depending on the scaffolding context, thereby defining mitogenic and anti‑apoptotic outcomes in different cell types. Sustained SP–NK‑1R activity promotes proliferation, migration, and survival of many tumor cell types, and NK‑1R is overexpressed in glioblastoma, neuroblastoma, pancreatic, colorectal, and breast carcinomas, where receptor activation supports oncogenic programs via MAPK, PI3K–Akt, and NF‑κB signaling; NK‑1R antagonists show antiproliferative effects in these models and are under evaluation as experimental anticancer agents. TGF‑β signaling modulates NK‑1R function in mucosal T cells by delaying ligand‑induced NK‑1R internalization and augmenting SP‑driven NF‑κB and AP‑1 activation, indicating cross‑talk between serine/threonine kinase receptors and NK‑1R that can intensify effector T‑cell cytokine production and mucosal inflammation.

Background

Neurokinin‑1 receptor (NK‑1R; TACR1) is the prototypic tachykinin G protein‑coupled receptor that displays highest affinity for substance P and lower affinity for neurokinin A, neurokinin B, hemokinin‑1 and endokinins, integrating neuropeptidergic, vascular, and immune signals across nervous, cardiovascular, gastrointestinal, and hematopoietic systems. NK‑1R is a class A seven‑transmembrane GPCR with three extracellular and three intracellular loops, an N‑terminal extracellular domain containing N‑linked glycosylation sites that stabilize the receptor at the plasma membrane, and a cytoplasmic C‑terminal tail enriched in serine/threonine residues that governs G‑protein coupling, β‑arrestin recruitment, desensitization, and internalization; alternative splicing generates a full‑length 407‑residue isoform and a truncated 311‑residue isoform lacking most of the C‑terminus with markedly different signaling properties. Substance P binding to full‑length NK‑1R preferentially engages Gq/11 proteins to activate phospholipase Cβ, driving hydrolysis of phosphatidylinositol 4,5‑bisphosphate into inositol 1,4,5‑trisphosphate and diacylglycerol, release of intracellular Ca²⁺, and protein kinase C activation; parallel coupling to Gs stimulates adenylyl cyclase, elevates cAMP, activates protein kinase A, and modulates CREB‑dependent transcription, while G12/13 linkage activates Rho/ROCK to control actomyosin contractility and membrane blebbing during migration. Downstream, NK‑1R signaling activates Ras/Raf/MEK/ERK and p38 MAPK cascades, PI3K–Akt pathways, and NF‑κB, leading to induction of immediate‑early genes (c‑fos, c‑myc), cell‑cycle regulators, and a spectrum of pro‑inflammatory mediators including IL‑1, IL‑6, IL‑8, TNF‑α, MIP‑1β and IFN‑γ that link neurogenic input to innate and adaptive immune responses. Full‑length NK‑1R efficiently couples to calcium mobilization, rapid and sustained ERK activation, NF‑κB activation, IL‑8 transcription, and PKCδ phosphorylation, whereas the truncated isoform displays roughly ten‑fold lower affinity for substance P, fails to mobilize calcium, does not activate NF‑κB or IL‑8, and shows delayed, attenuated ERK phosphorylation, reflecting loss of C‑terminal phosphorylation sites required for G protein‑coupled receptor kinase interaction and β‑arrestin‑scaffolded signalosomes. NK‑1R is widely expressed on sensory and autonomic neurons, astrocytes, microglia, and vascular endothelium where it mediates nociceptive transmission, neurogenic inflammation, vasodilation, and emesis, and is enriched in brainstem regions such as nucleus tractus solitarius and area postrema that control vomiting, providing the anatomical basis for the clinical efficacy of high‑affinity NK‑1R antagonists aprepitant and fosaprepitant in chemotherapy‑induced nausea and vomiting. The receptor is also expressed on monocytes, macrophages, dendritic cells, T and B lymphocytes, NK cells, and bone marrow progenitors, where substance P–NK‑1R signaling enhances chemotaxis, cytokine production, respiratory burst, and survival, thereby amplifying antibacterial, antiviral, and antifungal responses while contributing to chronic inflammatory pathology in disorders such as inflammatory bowel disease, arthritis, and airway hyper‑responsiveness. In the immune context, NK‑1R signaling in monocyte–macrophages and lymphocytes augments NF‑κB‑driven cytokine output and modulates expression of chemokine receptors including CCR5, with NK‑1R antagonists reducing HIV entry and replication in mononuclear phagocytes and peripheral blood mononuclear cells through down‑regulation of CCR5 and disruption of an SP‑driven feed‑forward loop. NK‑1R internalization, recycling, and signaling duration are tightly shaped by C‑terminal phosphorylation and β‑arrestin binding: full‑length NK‑1R forms β‑arrestin/Src/ERK complexes that can retain active ERK in the cytoplasm or enable nuclear translocation depending on the scaffolding context, thereby defining mitogenic and anti‑apoptotic outcomes in different cell types. Sustained SP–NK‑1R activity promotes proliferation, migration, and survival of many tumor cell types, and NK‑1R is overexpressed in glioblastoma, neuroblastoma, pancreatic, colorectal, and breast carcinomas, where receptor activation supports oncogenic programs via MAPK, PI3K–Akt, and NF‑κB signaling; NK‑1R antagonists show antiproliferative effects in these models and are under evaluation as experimental anticancer agents. TGF‑β signaling modulates NK‑1R function in mucosal T cells by delaying ligand‑induced NK‑1R internalization and augmenting SP‑driven NF‑κB and AP‑1 activation, indicating cross‑talk between serine/threonine kinase receptors and NK‑1R that can intensify effector T‑cell cytokine production and mucosal inflammation.

References
https://pubmed.ncbi.nlm.nih.gov/26421291/ https://pubmed.ncbi.nlm.nih.gov/35013118/

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%