التفاصيل البيبلوغرافية
| العنوان: |
Abstract 15402: P90 Ribosomal S6 Kinase Rescues Contractility of Myosin Light Chain Kinase Null Smooth Muscle |
| المؤلفون: |
Kalra, Jaspreet, Ayon, Ramon J, Markowska, Zaneta, Derewenda, Urszula, Sonkusare, Swapnil K, Somlyo, Avril V |
| المصدر: |
Circulation ; volume 146, issue Suppl_1 ; ISSN 0009-7322 1524-4539 |
| بيانات النشر: |
Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: |
2022 |
| الوصف: |
Introduction: Smooth muscle (SM) contraction is regulated by an increase in [Ca 2+ ] , activation of myosin light chain kinase (MLCK) and phosphorylation of myosin regulatory light chain (RLC 20 ) activating myosin crossbridge cycling. MLCK null mice die at birth, but SM retains the ability to contract suggesting the presence of another kinase(s). Based on studies with WT and p90 ribosomal S-6 kinase (RSK2) null mice, we reported that RSK2 activity accounts for ~ 25% of maximal contractile force in wild type (WT) resistance arteries. Hypothesis: RSK2 confers contractility via RLC 20 activation in smooth muscle cells of MLCK null mice. Methods: Tension was measured on E18 aorta, bladder, and umbilical artery from WT and MLCK -/- embryos, in response to phenylephrine, carbachol, high potassium, SM myosin phosphatase, calyculinA (10 uM), as well as Ca 2+ following permeabilization with α-toxin. VSMCs were cultured from E18 MLCK -/- aortae and from WT and RSK2 -/- mouse mesenteric arteries. Serum starved cells were stimulated with serum and LPA (0.5 uM), in the presence and absence of RSK2 inhibitor, LJH685 (10 μM). Protein-protein interactions were assessed by in-situ PLA assay and immunoprecipitation. On-going in-vitro studies using purified myosin and kinases address RSK2 direct regulation of MLCK activity. Results: Strips from bladder SM and umbilical artery from WT and MLCK -/- embryos (E18), contracted in response to agonists and high [K]. pCa-tension curves showed the same sensitivity to Ca 2+ in MLCK -/- and WT. Maximal force induced by calyculinA was also the same indicating an intact normal contractile apparatus in the MLCK -/- . Significant phosphorylation of RLC 20 at Ser19 occurred in LPA- and serum-stimulated MLCK -/- SM cells, which was significantly inhibited by the RSK2 inhibitor, LJH685 (n=3). PLA assay showed co-localization of RSK2 and MLCK (<40nm) (n=3). RSK2 is immunoprecipitated along with its activators ERK1/2, PDK1, suggestive of cross talk between RSK2 and MLCK on the actin filament ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1161/circ.146.suppl_1.15402 |
| الاتاحة: |
http://dx.doi.org/10.1161/circ.146.suppl_1.15402 |
| رقم الانضمام: |
edsbas.38D210C0 |
| قاعدة البيانات: |
BASE |