V. Cellular basis of action of GI peptides. Recent studies demonstrate a number of hormones and neurotransmitters that alter cell function by interacting with G-protein-coupled hepta- helical receptors can cause tyrosine phosphorylation similar to a number of growth factors, and this pathway may be involved in mediating these agent's growth effects. We examined both the ability of neuromedin B in C6 glioblastoma cells and NMB-R transfected cells and the ability of cholecystokinin (CCK) in rat pancreatic acini to cause tyrosine phosphorylation of p125 focal adhesion kinase (p125FAK), which plays an important role in mediating the growth effects of a number of neuropeptides. NMB cause rapid tyrosine phosphorylation of p125FAK in both cell types. The activation was not dependent on PKC activation or changes in [Ca2+]; because it was not altered by thapsigargin or PKC inhibitors. Cellular microfilaments but not microtubules were needed for p125FAK phosphorylation. Small GTP binding proteins mediated 50% of the NMB-mediated p125FAK phosphorylation because it was partially inhibited by clostridium botulinum C-3 toxin. CCK caused rapid p125FAK and paxillin phosphorylation through CCK/A receptors and the phosphorylation was mediated by activation of both high and low CCK affinity receptors. P125FAK phosphorylation by CCK did not require PKC or PLC activation. These studies show that activation of both the NMB-R and CCK/A-R can cause tyrosine phosphorylation of p125FAK, which may be an important mediator of the growth effects of these peptides.
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