Table 1.
Variable | pS474 PAK4 Phosphorylation | Concentrations and Incubation Times Reported In: |
Stimulation by pancreatic secretagogues | Fig. 2 | |
Yes | Endothelin-1, CCK-8, carbachol, bombesin | |
Stimulation by pancreatic growth factors | Fig. 2 | |
Yes | Insulin, IGF-1, HGF, EGF, bFGF, PDGF | |
Stimulation by post-receptor activators | Fig. 5 | |
Yes | TPA, thapsigargin, A23187 | |
Potency/Time course | Fig. 3 | |
EC50 of CCK-8 (nM) | 0.052 ± 0.003 | Fig. 3 |
EC50 of CCK-JMV (nM) | 0.10 ± 0.01 | Fig. 3 |
Inhibition of CCK-8-stimulated PAK4 activation | ||
Inhibition of 0.3 nM CCK-8 | Fig. 7 | |
Yes | p38 Inhibitor (SB202190), SFK inhibitor (PP2) | |
No | p44/42 inhibitor (PD98059) | |
Inhibition of 1 nM CCK-8 | Figs. 5–7 | |
Yes | PKD inhibitor (CRT0066101, kbNB142–70), PKC (GFX109203) | |
No | PI3K inhibitor (wortmannin, LY294002), Ca2+ (Thapsigargin) | |
Inhibition of 100 nM CCK-8 | Fig. 7 | |
Yes | p44/42 Inhibitor (PD98059) | |
No | p38 Inhibitor (SB202190), SFK Inhibitor (PP2) | |
Inhibition by PF-3758309 | Fig. 8 | |
PAK4 | From 0.1 nM (IC50: 1.89 ± 0.02 nM) | |
PAK2 | Requires high doses (i.e., ≥1 µM of PF-37580309) | |
Inhibition by LCH-7749944 | Fig. 9 | |
PAK4 | 90% decrease at 3 s incubation with 30 µM LCH-7749944 | |
PAK2 | No inhibition under these conditions |
Results are calculated from data shown in Figs. 2, 3, 5–9. bFGF, basic fibroblast growth factor; CCK, cholecystokinin; EGF, epidermal growth factor; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor 1; PAK, p21-activated kinase; PDGF, platelet-derived growth factor; SFK, Src family of kinases.