ArticleBiochimica et biophysica acta2015
Gastrointestinal hormones/neurotransmitters and growth factors can activate P21 activated kinase 2 in pancreatic acinar cells by novel mechanisms.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Role of serine/threonine phosphatases 1 and 2A in pancreatic acinar fluid and electrolyte secretion.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Interruption of cross-communication pathways alters the immune cell signature of pancreatic cancer and decreases tumor growth.Cell communication and signaling : CCS · 2026Article
- Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Review
- Application of Artificial Intelligence-Based Approaches in the Discovery and Development of Protein Kinase Inhibitors (PKIs) Targeting Anticancer Activity.Current topics in medicinal chemistry · 2025Review
- Cofilin activation in pancreatic acinar cells plays a pivotal convergent role for mediating CCK-stimulated enzyme secretion and growth.Frontiers in physiology · 2023Article
- Leptin activates Akt in oesophageal cancer cells via multiple atorvastatin-sensitive small GTPases.Molecular and cellular biochemistry · 2021Article
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- Group II p21-activated kinase, PAK4, is needed for activation of focal adhesion kinases, MAPK, GSK3, and β-catenin in rat pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Effect of P21-activated kinase 1 (PAK-1) inhibition on cancer cell growth, migration, and invasion.Pharmacology research & perspectives · 2019Article
- P21 activated kinase 2 promotes pancreatic cancer growth and metastasis.Oncology letters · 2019Article
- Inhibition of PAK1 alleviates cerulein-induced acute pancreatitis via p38 and NF-κB pathways.Bioscience reports · 2019Article
- Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2019Article
- P21-activated kinase 4 in pancreatic acinar cells is activated by numerous gastrointestinal hormones/neurotransmitters and growth factors by novel signaling, and its activation stimulates secretory/growth cascades.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Modulation of store-operated calcium entry and nascent adhesion by p21-activated kinase 1.Experimental & molecular medicine · 2018Article
- 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.Biochimica et biophysica acta · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
P-21-activated kinases (PAKs) are serine/threonine kinases comprising six isoforms divided in two groups, group-I (PAK1-3)/group-II (PAK4-6) which play important roles in cell cytoskeletal dynamics, survival, secretion and proliferation and are activated by diverse stimuli. However, little is known about PAKs ability to be activated by gastrointestinal (GI) hormones/neurotransmitters/growth-factors. We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/growth-factors to activate Group-I-PAKs and the signaling cascades involved. Only PAK2 was present in acini. PAK2 was activated by some pancreatic growth-factors [EGF, PDGF, bFGF], by secretagogues activating phospholipase-C (PLC) [CCK, carbachol, bombesin] and by post-receptor stimulants activating PKC [TPA], but not agents only mobilizing cellular calcium or increasing cyclic AMP. CCK-activation of PAK2 required both high- and low-affinity-CCK1-receptor-state activation. It was partially reduced by PKC- or Src-inhibition, but not with PI3K-inhibitors (wortmannin, LY294002) or thapsigargin. IPA-3, which prevents PAK2 binding to small-GTPases partially inhibited PAK2-activation, as well as reduced CCK-induced ERK1/2 activation and amylase release induced by CCK or bombesin. This study demonstrates pancreatic acini, possess only one Group-I-PAK, PAK2. CCK and other GI-hormones/neurotransmitters/growth-factors activate PAK2 via small GTPases (CDC42/Rac1), PKC and SFK but not cytosolic calcium or PI3K. CCK-activation of PAK2 showed several novel features being dependent on both receptor-activation states, having PLC- and PKC-dependent/independent components and small-GTPase-dependent/independent components. These results show that PAK2 is important in signaling cascades activated by numerous pancreatic stimuli which mediate their various physiological/pathophysiological responses and thus could be a promising target for the development of therapies in some pancreatic disorders such as pancreatitis.
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