P21 activated kinase4 in pancreatic acini is activated by GI hormones /growth factors by novel signaling and is needed to stimulate secretory/growth cascades.

P21 activated kinase4 in pancreatic acini is activated by GI hormones /growth factors by novel signaling and is needed to stimulate secretory/growth cascades. Am J Physiol Gastrointest Liver Physiol. 2018 Apr 19;: Authors: Ramos-Alvarez I, Jensen RT Abstract p21-activated kinases(PAKs) are highly conserved serine/threonine protein kinases, which are divided into two groups:Group-I(PAKs1-3) and Group-II(PAKs4-6). In various tissues, Group-II PAKs play important roles in cytoskeletal dynamics, cell growth as well as neoplastic development/progression. However, little is known about Group-II PAKs role in a number of physiological events including their ability to be activated by gastrointestinal(GI) hormones/neurotransmitters/growth-factors(GFs). We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/GFs to activate Group-II-PAKs and the signaling cascades involved. Only PAK4 was detected in pancreatic acini. PAK4 was activated by secretagogues stimulating phospholipase C(PLC)[Bombesin,CCK-8],by pancreatic-GFs(Insulin, IGF-1,HGF,EGF,bFGF,PDGF) and by post-receptor stimulants[TPA,A23187]. CCK-8 activation of PAK4 required both high- and low-affinity-CCK1-receptor-state activation. It was reduced by PKC-,Src-,p44/42- or p38-inhibition, but not with PI3K-inhibitors and only minimally by thapsigargin. A PKD-inhibitor completely inhibited CCK-8-stimulated PKC-activation, however, stimulated PAK4 phosphorylation ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research