کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815652 | 1058493 | 2010 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of a novel MK3 splice variant from murine ventricular myocardium
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کلمات کلیدی
nESMK5FPLCMBPDTTTX-100GSTMK2PKINLSERKPMSFPAGEDMSO - DMSOMAPK - MAPKp38 MAPK - P38 MAPKpolyacrylamide gel electrophoresis - الکتروفورز ژل پلی آکریل آمیدTriton X-100 - تریتون X-100 Alternative splicing - جابجایی جایگزینdithiothreitol - دیتیوتریتولDimethylsulfoxide - دیمتیل سولفواکسیدfast protein liquid chromatography - سریع کروماتوگرافی مایع پروتئینnuclear export signal - سیگنال صادرات هسته ایnuclear localization signal - سیگنال محلی سازی هسته ایphenylmethylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدPost-transcriptional regulation - مقررات پست مدرنMyelin basic protein - پروتئین پایه میلینmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenextracellular signal-related kinase - کیناز مرتبط با سیگنال خارج سلولیglutathione S-transferase - گلوتاتیون S-ترانسفراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
p38 MAP kinase (MAPK) isoforms α, β, and γ, are expressed in the heart. p38α appears pro-apoptotic whereas p38β is pro-hypertrophic. The mechanisms mediating these divergent effects are unknown; hence elucidating the downstream signaling of p38 should further our understanding. Downstream effectors include MAPK-activated protein kinase (MK)-3, which is expressed in many tissues including skeletal muscles and heart. We cloned full-length MK3 (MK3.1, 384 aa) and a novel splice variant (MK3.2, 266 aa) from murine heart. For MK3.2, skipping of exons 8 and 9 resulted in a frame-shift in translation of the first 85 base pairs of exon 10 followed by an in-frame stop codon. Of 3 putative phosphorylation sites for p38 MAPK, only Thr-203 remained functional in MK3.2. In addition, MK3.2 lacked nuclear localization and export signals. Quantitative real-time PCR confirmed the presence of these mRNA species in heart and skeletal muscle; however, the relative abundance of MK3.2 differed. Furthermore, whereas total MK3 mRNA was increased, the relative abundance of MK3.2 mRNA decreased in MK2â/â mice. Immunoblotting revealed 2 bands of MK3 immunoreactivity in ventricular lysates. Ectopically expressed MK3.1 localized to the nucleus whereas MK3.2 was distributed throughout the cell; however, whereas MK3.1 translocated to the cytoplasm in response to osmotic stress, MK3.2 was degraded. The p38α/β inhibitor SB203580 prevented the degradation of MK3.2. Furthermore, replacing Thr-203 with alanine prevented the loss of MK3.2 following osmotic stress, as did pretreatment with the proteosome inhibitor MG132. In vitro, GST-MK3.1 was strongly phosphorylated by p38α and p38β, but a poor substrate for p38δ and p38γ. GST-MK3.2 was poorly phosphorylated by p38α and p38β and not phosphorylated by p38δ and p38γ. Hence, differential regulation of MKs may, in part, explain diverse downstream effects mediated by p38 signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 10, October 2010, Pages 1502-1512
Journal: Cellular Signalling - Volume 22, Issue 10, October 2010, Pages 1502-1512
نویسندگان
Nadège Moïse, Dharmendra Dingar, Aida M. Mamarbachi, Louis R. Villeneuve, Nada Farhat, Matthias Gaestel, Maya Khairallah, Bruce G. Allen,