Telokin is an acidic protein with a sequence identical to the COOH-terminal domain of myosin light chain kinase (MLCK) produced by an alternate promoter of the MLCK gene. Although it is abundantly expressed in smooth muscle, its physiological function is not understood. In the present study, we attempted to clarify the function of telokin by analyzing its spatial and temporal localization in living single smooth muscle cells. Primary cultured smooth muscle cells were transfected with green fluorescent protein (GFP)-tagged telokin. The telokin-GFP localized mostly diffusely in cytosol. Stimulation with both sodium nitroprusside (SNP) and 8-bromo-cyclic GMP induced translocation of GFP-tagged telokin to near plasma membrane in living single smooth muscle cells. The translocation was slow, and it took more than 10 min at room temperature. Mutation of the phosphorylation sites of telokin (S13A, S19A, and S13A/S19A) significantly attenuated SNP-induced translocation. Both KT-5823 (cGMP-dependent protein kinase inhibitor) and PD-98059 (mitogen-activated protein kinase inhibitor) diminished the telokin-GFP translocation. These results suggest that telokin changes its intracellular localization because of phosphorylation at Ser13 and/or Ser19 via the cGMP-signaling pathway.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajpcell.00501.2001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ECM Modifications Driven by Age and Metabolic Stress Directly Promote the Vascular Smooth Muscle Cell Osteogenic Processes.
Arterioscler Thromb Vasc Biol
January 2025
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, United Kingdom. (M.W., M.F., R.O., L.S., M.M., C.M.S.).
Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.
Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.
The Role of Intravenous Selexipag in Managing PAH and Bridging Gaps in Oral Treatment: A Narrative Review.
Ther Clin Risk Manag
January 2025
Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA.
Pulmonary arterial hypertension (PAH) is a rare and potentially fatal condition characterized by progressive increases in blood pressure in the arteries of the lungs. Oral selexipag, approved by the Food and Drug Administration (FDA) in 2015 for the treatment of PAH, targets prostacyclin receptors on pulmonary arterial vascular smooth muscle and endothelial cells to improve blood flow through the lungs and reduce pulmonary vascular resistance. Oral selexipag is effective, but may be discontinued due to factors like side effects, emergency conditions, or inability to take oral medication, potentially leading to severe adverse events, such as rebound pulmonary hypertension and right heart failure.
View Article and Find Full Text PDFAsthma-associated prostate enlargement and bladder smooth muscle hypercontractility: unveiling a potential link to LUTS.
BMC Urol
January 2025
Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
Background: In male patients, benign prostate hyperplasia (BPH) and overactive bladder (OAB) secondary to BPH are the primary causes of Lower Urinary Tract Symptoms (LUTS). Recent clinical studies have reported an increased risk of LUTS, particularly severe LUTS conditions, in male asthmatic patients. However, the potential link and mechanism remain unclear.
View Article and Find Full Text PDFSingle-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis.
Nat Commun
January 2025
Interfakultäres Institut für Biochemie, University of Tübingen, Tübingen, Germany.
A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions.
View Article and Find Full Text PDFVascular biology and medicine: amyloid-beta alterations in neurocardiovascular diseases and new targets to treat smooth muscle cell dysfunction.
Eur Heart J
January 2025
Center of Excellence of Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!