ArticleThe Journal of biological chemistry2010
The Lbc Rho guanine nucleotide exchange factor α-catulin axis functions in serotonin-induced vascular smooth muscle cell mitogenesis and RhoA/ROCK activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Catulin reporter marks a heterogeneous population of invasive breast cancer cells with some demonstrating plasticity and participating in vascular mimicry.Scientific reports · 2022Article
- Novel hub genes associated with pulmonary artery remodeling in pulmonary hypertension.Frontiers in cardiovascular medicine · 2022Article
- Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.Pharmacology & therapeutics · 2019Review
- Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.The Lancet. Respiratory medicine · 2017Article
- RNA-seq analysis provide new insights into mapk signaling of apolipoproteinciii-induced inflammation in porcine vascular endothelial cells.Cell cycle (Georgetown, Tex.) · 2017Article
- Mice Deficient in AKAP13 (BRX) Are Osteoporotic and Have Impaired Osteogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Article
- The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.The Biochemical journal · 2014Article
- Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension.Small GTPases · 2014Review
- Mineralocorticoid receptor antagonism attenuates experimental pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- L-tryptophan metabolism in pregnant mice fed a high L-tryptophan diet and the effect on maternal, placental, and fetal growth.International journal of tryptophan research : IJTR · 2013Article
- α-Catulin marks the invasion front of squamous cell carcinoma and is important for tumor cell metastasis.Molecular cancer research : MCR · 2012Article
- Alpha-dystrobrevin-1 recruits alpha-catulin to the alpha1D-adrenergic receptor/dystrophin-associated protein complex signalosome.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Individual protomers of a G protein-coupled receptor dimer integrate distinct functional modules.Cell discoveryArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) is mitogenic for several cell types including pulmonary arterial smooth muscle cells (PASMC), and is associated with the abnormal vascular smooth muscle remodeling that occurs in pulmonary arterial hypertension. RhoA/Rho kinase (ROCK) function is required for 5-HT-induced PASMC mitogenesis, and 5-HT activates RhoA; however, the signaling steps are poorly defined. Rho guanine nucleotide exchange factors (Rho GEFs) transduce extracellular signals to Rho, and we found that 5-HT treatment of PASMC led to increased membrane-associated Lbc Rho GEF, suggesting modulation by 5-HT. Lbc knockdown by siRNA attenuated 5-HT-induced thymidine uptake in PASMC, indicating a role in PASMC mitogenesis. 5-HT triggered Rho-dependent serum response factor-mediated reporter activation in PASMC, and this was reduced by Lbc depletion. Lbc knockdown reduced 5-HT-induced RhoA/ROCK activation, but not p42/44 ERK MAP kinase activation, suggesting that Lbc is an intermediary between 5-HT and RhoA/ROCK, but not ERK. 5-HT stimulation of PASMC led to increased association between Lbc, RhoA, and the α-catulin scaffold. Furthermore, α-catulin knockdown attenuated 5-HT-induced PASMC thymidine uptake. 5-HT-induced PASMC mitogenesis was reduced by dominant-negative G(q) protein, suggesting cooperation with Lbc/α-catulin. These results for the first time define a Rho GEF involved in vascular smooth muscle cell growth and serotonin signaling, and suggest that Lbc Rho GEF family members play distinct roles. Thus, the Lbc/α-catulin axis participates in 5-HT-induced PASMC mitogenesis and RhoA/ROCK signaling, and may be an interventional target in diseases involving vascular smooth muscle remodeling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.