Integration of Rap1 and Calcium Signaling

Kosuru, Ramoji; Chrzanowska‐Wodnicka, Magdalena

doi:10.3390/ijms21051616

Cited by 37 publications

(32 citation statements)

References 146 publications

(226 reference statements)

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“…Rap1a is a member of the small GTPases of the Ras family, and is involved in effector-induced phagocytosis regulation in macrophages 39 . There is growing evidence that Rap1 produced in excess as a cause for vascular remodeling and inflammation leads to the progression of atherosclerosis 40 . According to our gene chip analysis, Rap1a is involved in the FABP4-mediated Hcy-induced macrophage inflammation.…”

Section: Resultsmentioning

confidence: 99%

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Zhang

Wang

et al. 2022

Laboratory Investigation

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Atherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)—a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE−/− mice.

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Section: Resultsmentioning

confidence: 99%

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Zhang

Wang

et al. 2022

Laboratory Investigation

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“…In addition, there was a close connection between cAMP signaling pathway and Rap1 signaling pathway. Rap1 couples extracellular stimulation with intracellular signaling through cAMP, diacylglycerol (DAG), and calcium ion and controls the important cellular functions, including shaping neurons (Kosuru and Chrzanowska, 2020).…”

Section: Critical Pathways and Genes Involved In The Growth Of Cynogl...mentioning

confidence: 99%

Identification of lncRNA-miRNA-mRNA Network Involved in Sexual Size Dimorphism of Chinese Tongue Sole (Cynoglossus semilaevis)

Wang

Yang

et al. 2022

Front. Mar. Sci.

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Chinese tongue sole (Cynoglossus semilaevis) is a flatfish species unique to Northeast Asia, exhibiting the typical female-biased sexual size dimorphism (SSD). To explore the possible regulatory roles of non-coding RNAs (ncRNAs) on this phenomenon, whole transcriptomic analysis was performed by using female, male, and pseudomale C. semilaevis to identify differentially expressed (DE) long ncRNAs (DE lncRNAs), microRNA (DE miRNAs), and differentially expressed genes (DEGs) from the brain, gonad, liver, and muscle tissues. Most of them were concentrated in the gonad and muscle, and the gene expression patterns of pseudomale individuals were similar to male individuals. The association of DE lncRNAs and target messenger RNAs (mRNAs) was predicted based on antisense, cis-, and trans-regulatory mechanisms, with enriched protein digestion and absorption, cyclic adenosine monophosphate (cAMP) signaling pathway, sulfur metabolism, cell cycle, and splicesome (p < 0.05). Furthermore, weighted gene co-expression network analysis (WGCNA) was employed to cluster the expression patterns of DE lncRNA, and two modules (greenyellow and blue) had the highest positive and negative correlations with growth traits, respectively. Importantly, the female-biased expression in the greenyellow module and the male- and pseudomale-biased expression in the blue module were observed in the gonad. The target gene analysis for DE miRNA revealed 3,034 mRNA-miRNA pairs with the opposite expression patterns. Finally, the lncRNA-miRNA-mRNA network, including 385 DE lncRNAs, 138 DE miRNAs, and 456 DEGs, was constructed. Among which, 78 DE lncRNAs, 12 DE miRNAs, and 13 DEGs involved in cell growth and death pathway were related to the SSD of C. semilaevis. This study described the lncRNA-miRNA-mRNA regulatory network in the SSD of C. semilaevis for the first time. The functional prediction analysis suggested that these DE lncRNAs and DE miRNAs might be involved in flatfish SSD by regulating several potential growth-related pathways (e.g., cell cycle, cAMP signaling, and Rap1 signaling). Further studies related to these ncRNAs will enlarge our understanding of the regulatory effects of ncRNAs on fish SSD.

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“…the transcription factor CREB 55,56 . Inhibition of PKC γ, CaMKII, MAPK, and CREB can suppress the generation and maintenance of neuropathic pain 57 .…”

Section: Discussionmentioning

confidence: 99%

The dopamine D1–D2DR complex in the rat spinal cord promotes neuropathic pain by increasing neuronal excitability after chronic constriction injury

et al. 2021

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Dopamine D1 receptor (D1DR) and D2 receptor (D2DR) are closely associated with pain modulation, but their exact effects on neuropathic pain and the underlying mechanisms remain to be identified. Our research revealed that intrathecal administration of D1DR and D2DR antagonists inhibited D1–D2DR complex formation and ameliorated mechanical and thermal hypersensitivity in chronic constriction injury (CCI) rats. The D1–D2DR complex was formed in the rat spinal cord, and the antinociceptive effects of D1DR and D2DR antagonists could be reversed by D1DR, D2DR, and D1–D2DR agonists. Gαq, PLC, and IP3 inhibitors also alleviated CCI-induced neuropathic pain. D1DR, D2DR, and D1–D2DR complex agonists all increased the intracellular calcium concentration in primary cultured spinal neurons, and this increase could be reversed by D1DR, D2DR antagonists and Gαq, IP3, PLC inhibitors. D1DR and D2DR antagonists significantly reduced the expression of p-PKC γ, p-CaMKII, p-CREB, and p-MAPKs. Levo-corydalmine (l-CDL), a monomeric compound in Corydalis yanhusuo W.T. Wang, was found to obviously suppress the formation of the spinal D1–D2DR complex to alleviate neuropathic pain in CCI rats and to decrease the intracellular calcium concentration in spinal neurons. l-CDL-induced inhibition of p-PKC γ, p-MAPKs, p-CREB, and p-CaMKII was also reversed by D1DR, D2DR, and D1–D2DR complex agonists. In conclusion, these results indicate that D1DR and D2DR form a complex and in turn couple with the Gαq protein to increase neuronal excitability via PKC γ, CaMKII, MAPK, and CREB signaling in the spinal cords of CCI rats; thus, they may serve as potential drug targets for neuropathic pain therapy.

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Integration of Rap1 and Calcium Signaling

Cited by 37 publications

References 146 publications

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Identification of lncRNA-miRNA-mRNA Network Involved in Sexual Size Dimorphism of Chinese Tongue Sole (Cynoglossus semilaevis)

The dopamine D1–D2DR complex in the rat spinal cord promotes neuropathic pain by increasing neuronal excitability after chronic constriction injury

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