ArticleAmerican journal of physiology. Cell physiology2011
Lysophosphatidic acid 5 receptor induces activation of Na(+)/H(+) exchanger 3 via apical epidermal growth factor receptor in intestinal epithelial cells.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 43 citations in OpenAlex.
- Survival of Stem Cells and Progenitors in the Intestine Is Regulated by LPACellular and molecular gastroenterology and hepatology · 2022Article
- The recycling regulation of sodium-hydrogen exchanger isoform 3(NHE3) in epithelial cells.Cell cycle (Georgetown, Tex.) · 2021Review
- Lysophosphatidic Acid Receptor 5 (LPAR5) Plays a Significance Role in Papillary Thyroid Cancer via Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Trefoil factor 2 activation of CXCR4 requires calcium mobilization to drive epithelial repair in gastric organoids.The Journal of physiology · 2019Article
- Autotaxin determines colitis severity in mice and is secreted by B cells in the colon.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.Cellular and molecular life sciences : CMLS · 2018Article
- Adenosinergic signaling inhibits oxalate transport by human intestinal Caco2-BBE cells through the AAmerican journal of physiology. Cell physiology · 2018Article
- Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- SLC9 Gene Family: Function, Expression, and Regulation.Comprehensive Physiology · 2018Review
- EGFR as a Negative Regulatory Protein Adjusts the Activity and Mobility of NHE3 in the Cell Membrane of IPEC-J2 Cells With TGEV Infection.Frontiers in microbiology · 2018Article
- Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated CaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018Review
- Article
- Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss.The Journal of clinical investigation · 2015Article
- Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2.American journal of physiology. Cell physiology · 2015Article
- Diverse roles of LPA signaling in the intestinal epithelium.Experimental cell research · 2015Review
- Autotaxin-LPA receptor axis in the pathogenesis of lung diseases.International journal of clinical and experimental medicine · 2015Review
- Lysophosphatidic acid stimulation of NHE3 exocytosis in polarized epithelial cells occurs with release from NHERF2 via ERK-PLC-PKCδ signaling.American journal of physiology. Cell physiology · 2014Article
- Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Extracellular nucleotides inhibit oxalate transport by human intestinal Caco-2-BBe cells through PKC-δ activation.American journal of physiology. Cell physiology · 2013Article
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4 authors at 1 institution in 1 country.
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Abstract
Na(+) absorption is a vital process present in all living organisms. We have reported previously that lysophosphatidic acid (LPA) acutely stimulates Na(+) and fluid absorption in human intestinal epithelial cells and mouse intestine by stimulation of Na(+)/H(+) exchanger 3 (NHE3) via LPA(5) receptor. In the current study, we investigated the mechanism of NHE3 activation by LPA(5) in Caco-2bbe cells. LPA(5)-dependent activation of NHE3 was blocked by mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 and U0126, but not by phosphatidylinositol 3-kinase inhibitor LY294002 or phospholipase C-β inhibitor U73122. We found that LPA(5) transactivated the epidermal growth factor receptor (EGFR) and that inhibition of EGFR blocked LPA(5)-dependent activation of NHE3, suggesting an obligatory role of EGFR in the NHE3 regulation. Confocal immunofluorescence and surface biotinylation analyses showed that LPA(5) was located mostly in the apical membrane. EGFR, on the other hand, showed higher expression in the basolateral membrane. However, inhibition of apical EGFR, but not basolateral EGFR, abrogated LPA-induced regulation of MEK and NHE3, indicating that LPA(5) selectively activates apical EGFR. Furthermore, transactivation of EGFR independently activated the MEK-ERK pathway and proline-rich tyrosine kinase 2 (Pyk2). Similarly to MEK inhibition, knockdown of Pyk2 blocked activation of NHE3 by LPA. Furthermore, we showed that RhoA and Rho-associated kinase (ROCK) are involved in activation of Pyk2. Interestingly, LPA(5) did not directly activate RhoA but was required for transactivation of EGFR. Together, these results unveil a pivotal role of apical EGFR in NHE3 regulation by LPA and show that the RhoA-ROCK-Pyk2 and MEK-ERK pathways converge onto NHE3.
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