کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259269 | 1534633 | 2016 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events
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کلمات کلیدی
GSK3-βMARCKSPKCSFKPAKPLCPYK2MAP kinase kinaseCCKSHCpKaRAF12-O-tetradecanoylphorbol-13-acetateCASFAKHRPHGFtPAc-Jun-N-terminal kinaseJnkPKDPAK2p21-Activated kinasesPI3KMAPK/ERK - MAPK / ERKROS - ROSmyristoylated alanine-rich C kinase substrate - Substrate C kinase غنی از آلانین myristoylatedPancreatic acini - آکانی پانکراسAkt - آکتCrk-associated substrate - بستر مرتبط با Crkproline-rich tyrosine kinase 2 - تریستین کیناز غنی از پرولین 2Gastrointestinal - دستگاه گوارشSignaling - سیگنالینگHepatocyte growth factor - عامل رشد هپاتوسیتdominant negative - غالب منفی استphosphatase and tensin homolog - فسفاتاز و تنسین همولوگphospholipase C - فسفولیپاز CMEK - مجاهدین خلقCell death - مرگ سلولی Pancreatitis - پانکراتیتHorseradish peroxidase - پراکسیداز هوررادیشprotein kinase A - پروتئین کیناز Aprotein kinase B - پروتئین کیناز Bprotein kinase D - پروتئین کیناز DProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPten - ژن PTENCbl - کلمfocal adhesion kinase - کیناز چسبندگی کانونیglycogen synthase kinase 3 - گلیکوزین سنتاز کیناز 3Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events](/preview/png/8259269.png)
چکیده انگلیسی
In a recent study we explored Group-1-p21-activated kinases (GP.1-PAKs) in rat pancreatic acini. Only PAK2 was present; it was activated by gastrointestinal-hormones/neurotransmitters and growth factors in a PKC-, Src- and small-GTPase-mediated manner. PAK2 was required for enzyme-secretion and ERK/1-2-activation. In the present study we examined PAK2's role in CCK and TPA-activation of important distal signaling cascades mediating their physiological/pathophysiological effects and analyzed its role in pathophysiological processes important in early pancreatitis. In rat pancreatic acini, PAK2-inhibition by the specific, GP.1.PAK-inhibitor, IPA-3-suppressed cholecystokinin (CCK)/TPA-stimulated activation of focal-adhesion kinases and mitogen-activated protein-kinases. PAK2-inhibition reversed the dual stimulatory/inhibitory effect of CCK/TPA on the PI3K/Akt/GSK-3β pathway. However, its inhibition did not affect PKC activation. PAK2-inhibition protected acini from CCK-induced ROS-generation; caspase/trypsin-activation, important in early pancreatitis; as well as from cell-necrosis. Furthermore, PAK2-inhibition reduced proteolytic-activation of PAK-2p34, which is involved in programmed-cell-death. To ensure that the study did not only rely in the specificity of IPA-3 as a PAK inhibitor, we used two other approaches for PAK inhibition, FRAX597 a ATP-competitive-GP.1-PAKs-inhibitor and infection with a PAK2-dominant negative(DN)-Advirus. Those two approaches confirmed the results obtained with IPA-3. This study demonstrates that PAK2 is important in mediating CCK's effect on the activation of signaling-pathways known to mediate its physiological/pathophysiological responses including several cellular processes linked to the onset of pancreatitis. Our results suggest that PAK2 could be a new, important therapeutic target to consider for the treatment of diseases involving deregulation of pancreatic acinar cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 6, June 2016, Pages 1122-1136
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 6, June 2016, Pages 1122-1136
نویسندگان
Bernardo Nuche-Berenguer, Irene Ramos-Álvarez, R.T. Jensen,