Role of G protein-coupled vasoactive intestinal peptide receptors in HIV integration

The role of protein kinase C (PKC) in sustained contraction was examined in intestinal circular and longitudinal muscle cells. Initial contraction induced by agonists (CCK-8 and neuromedin C) was abolished by 1) inhibitors of Ca2+ mobilization (neomycin and dimethyleicosadienoic acid), 2) calmidazolium, and 3) myosin light chain (MLC) kinase (MLCK) inhibitor KT-5926. In contrast, sustained contraction was not affected by these inhibitors but was abolished by 1) the PKC inhibitors chelerythrine and calphostin C, 2) PKC-ε antibody, and 3) a pseudosubstrate PKC-ε inhibitor. GDPβS abolished both initial and sustained contraction, whereas a Gαq/11 antibody inhibited only initial contraction, implying that sustained contraction was dependent on activation of a distinct G protein. Sustained contraction induced by epidermal growth factor was inhibited by calphostin C, PKC-α,β,γ antibody, and a pseudosubstrate PKC-α inhibitor. Ca2+ (0.4 μM) induced an initial contraction in permeabilized muscle cells that was blocked by calmodulin and MLCK inhibitors and a sustained contraction that was blocked by calphostin C and a PKC-α,β,γ antibody. Thus initial contraction induced by Ca2+, agonists, and growth factors is mediated by MLCK, whereas sustained contraction is mediated by specific Ca2+-dependent and -independent PKC isozymes. G protein-coupled receptors are linked to PKC activation via distinct G proteins.

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G-protein–coupled formyl peptide receptors play a dual role in neutrophil chemotaxis and bacterial phagocytosis

Molecular Biology of the Cell ◽

10.1091/mbc.e18-06-0358 ◽

2019 ◽

Vol 30 (3) ◽

pp. 346-356 ◽

Cited By ~ 7

Author(s):

Xi Wen ◽

Xuehua Xu ◽

Wenxiang Sun ◽

Keqiang Chen ◽

Miao Pan ◽

...

Keyword(s):

G Protein ◽

Receptor Tyrosine Kinase ◽

Tyrosine Kinases ◽

Actin Polymerization ◽

G Protein Coupled Receptors ◽

Peptide Receptors ◽

Tyrosine Kinase Signaling ◽

Formyl Peptide Receptors ◽

Formyl Peptide ◽

G Protein Coupled

A dogma of innate immunity is that neutrophils use G-protein–coupled receptors (GPCRs) for chemoattractant to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work showed that G-protein–coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2–/–) are defective in the phagocytosis of Escherichia coli and the chemoattractant N-formyl-Met-Leu-Phe (fMLP)-coated beads. fMLP immobilized onto the surface of a bead interacts with FPRs, which trigger a Ca2+response and induce actin polymerization to form a phagocytic cup for engulfment of the bead. This chemoattractant GPCR/Gi signaling works independently of phagocytic receptor/tyrosine kinase signaling to promote phagocytosis. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight against invading bacteria.

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