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Human Substance P Receptor Lacking The C‐terminal Domain Remains Competent To Desensitize And Internalize

M. D. Richardson, A. Balius, Keisuke Yamaguchi, Emily R Freilich, L. Barak, M. Kwatra
Published 2003 · Biology, Medicine

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Substance P receptor (SPR) and its naturally occurring splice‐variant, lacking the C‐terminal tail, are found in brain and spinal cord. Whether C‐terminally truncated SPR desensitizes like full‐length SPR is controversial. We used a multivaried approach to determine whether human SPR (hSPR) and a C‐terminally truncated mutant, hSPRΔ325, differ in their desensitization and internalization. In HEK‐293 cells expressing either hSPRΔ325 or hSPR, SP‐induced desensitization of the two receptors was similar when measured by inositol triphosphate accumulation or by transient translocation of coexpressed PKCβII‐GFP to the plasma membrane. Moreover, translocation of β‐arrestin 1 or 2‐GFP (βarr1‐GFP or βarr2‐GFP) to the plasma membrane, and receptor internalization were also similar. However, hSPR and hSPRΔ325 differ in their phosphorylation and in their ability to form β‐arrestin‐containing endocytic vesicles. Unlike hSPR, hSPRΔ325 is not phosphorylated to a detectable level in intact HEK293 cells, and whereas hSPR forms vesicles containing either βarr1‐GFP or βarr2‐GFP, hSPRΔ325 does not form any vesicles with βarr1‐GFP, and forms fewer vesicles with βarr2‐GFP. We conclude that truncated hSPR undergoes agonist‐dependent desensitization and internalization without detectable receptor phosphorylation.
This paper references
Molecular characterization of a functional cDNA for rat substance P receptor.
Y. Yokota (1989)
Molecular cloning, structural characterization and functional expression of the human substance P receptor.
Y. Takeda (1991)
A potent nonpeptide antagonist of the substance P (NK1) receptor.
R. M. Snider (1991)
Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.
Y. Nishizuka (1992)
Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.
T. Fong (1992)
Functional nonequivalence of structurally homologous domains of neurokinin-1 and neurokinin-2 type tachykinin receptors.
P. Blount (1993)
Prolonged desensitization of the human endothelin A receptor in Xenopus oocytes. Comparative studies with the human neurokinin A receptor.
C. Cyr (1993)
A luteinizing hormone receptor with a severely truncated cytoplasmic tail (LHR-ct628) desensitizes to the same degree as the full-length receptor.
X. Zhu (1993)
Attenuation of agonist‐induced desensitization of the rat substance P receptor by progressive truncation of the C‐terminus
N. Sasakawa (1994)
Similar Rates of Phosphatidylinositol Hydrolysis Following Activation of Wild‐Type and Truncated Rat Neurokinin‐1 Receptors
R. Raddatz (1995)
Localization of protein kinases by anchoring proteins: a theme in signal transduction.
D. Mochly-Rosen (1995)
Truncation of the receptor carboxyl terminus impairs membrane signaling but not ligand binding of human ETB endothelin receptor.
T. Koshimizu (1995)
Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo
P. Mantyh (1996)
Dynamin and β-Arrestin Reveal Distinct Mechanisms for G Protein-coupled Receptor Internalization*
Jie Zhang (1996)
Neurogenic Amplification of Immune Complex Inflammation
C. Bozic (1996)
A β-Arrestin/Green Fluorescent Protein Biosensor for Detecting G Protein-coupled Receptor Activation*
L. Barak (1997)
A substance P (neurokinin-1) receptor mutant carboxyl-terminally truncated to resemble a naturally occurring receptor isoform displays enhanced responsiveness and resistance to desensitization.
H. Li (1997)
Identification of Potential Tyrosine-containing Endocytic Motifs in the Carboxyl-tail and Seventh Transmembrane Domain of the Neurokinin 1 Receptor*
S. Böhm (1997)
Altered nociception, analgesia and aggression in mice lacking the receptor for substance P
C. Felipe (1998)
Human substance P receptor expressed in Sf9 cells couples with multiple endogenous G proteins.
K. Nishimura (1998)
Visualization of Dynamic Trafficking of a Protein Kinase C βII/Green Fluorescent Protein Conjugate Reveals Differences in G Protein-coupled Receptor Activation and Desensitization*
Xiao Feng (1998)
Substance P receptor immunodetection in the spinal cord: comparative use of direct anti-receptor antibody and anti-complementary peptide antibody
F. Zerari (1998)
Desensitization of the neurokinin-1 receptor (NK1-R) in neurons: effects of substance P on the distribution of NK1-R, Galphaq/11, G-protein receptor kinase-2/3, and beta-arrestin-1/2.
K. McConalogue (1998)
The role of receptor kinases and arrestins in G protein-coupled receptor regulation.
J. Krupnick (1998)
Characterization of GRK2-catalyzed phosphorylation of the human substance P receptor in Sf9 membranes.
K. Nishimura (1998)
Phosphorylation Is Not Required for Dynamin-dependent Endocytosis of a Truncated Mutant Opioid Receptor*
S. Murray (1998)
Cellular Trafficking of G Protein-coupled Receptor/β-Arrestin Endocytic Complexes*
J. Zhang (1999)
Real-time Visualization of the Cellular Redistribution of G Protein-coupled Receptor Kinase 2 and β-Arrestin 2 during Homologous Desensitization of the Substance P Receptor*
Larry S. Barak (1999)
Substance P-induced trafficking of beta-arrestins. The role of beta-arrestins in endocytosis of the neurokinin-1 receptor.
K. McConalogue (1999)
Phosphorylation-independent inhibition of parathyroid hormone receptor signaling by G protein-coupled receptor kinases.
F. Dicker (1999)
Characterization of differences between rapid agonist-dependent phosphorylation and phorbol ester-mediated phosphorylation of human substance P receptor in intact cells.
E. Roush (1999)
Association of β-Arrestin with G Protein-coupled Receptors during Clathrin-mediated Endocytosis Dictates the Profile of Receptor Resensitization*
Robert H. Oakley (1999)
Regulation of Muscarinic Acetylcholine Receptor Sequestration and Function by β-Arrestin*
O. Vögler (1999)
Substance P-induced trafficking
K. McConalogue (1999)
Differential Affinities of Visual Arrestin, βArrestin1, and βArrestin2 for G Protein-coupled Receptors Delineate Two Major Classes of Receptors*
R. Oakley (2000)
Differential Expression of Neurokinin-1 Receptor by Human Mucosal and Peripheral Lymphoid Cells
T. Goode (2000)
Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling.
S. Ferguson (2001)
Molecular Determinants Underlying the Formation of Stable Intracellular G Protein-coupled Receptor-β-Arrestin Complexes after Receptor Endocytosis*
R. H. Oakley (2001)
Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine2A receptor desensitization and resensitization reveal an arrestin-, GRK2-, and GRK5-independent mode of regulation in human embryonic kidney 293 cells
J. Gray (2001)
The Dynamin-dependent, Arrestin-independent Internalization of 5-Hydroxytryptamine 2A (5-HT2A) Serotonin Receptors Reveals Differential Sorting of Arrestins and 5-HT2A Receptors during Endocytosis* 210
A. Bhatnagar (2001)
The dynamin-dependent, arrestinindependent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis
A. Bhatnagar (2001)
Aspartic Acid 564 in the Third Cytoplasmic Loop of the Luteinizing Hormone/Choriogonadotropin Receptor Is Crucial for Phosphorylation-independent Interaction with Arrestin2*
S. Mukherjee (2002)
The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals.
L. Luttrell (2002)
The role of b-arrestins in the termination and transduction of G-protein-coupled receptor
L M.Luttrell (2002)

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V. Lukashova (2011)
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C. Walther (2010)
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M. Rankin (2010)
A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor‐mediated apoptosis in glioblastomas
T. Akazawa (2009)
Substance P (SP) enhances CCL5‐induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin‐1 receptor (NK1R)
I. Chernova (2009)
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Feifei Wang (2008)
Inhibitory effect of the substance P and its derivative on erythropoietin-independent growth of erythroid progenitors in polycythemia vera.
C. Le Gall (2008)
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C. Choi (2008)
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A. Tobin (2008)
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F. Wang (2008)
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Tom Kershaw (2008)
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