Cholecystokinin-B/gastrin receptors mediate rapid formation of actin stress fibers.
Specific receptors for brain-gut peptide hormones, cholecystokinin (CCK) and gastrin, are expressed in a variety of human tumor cells. CCK and gastrin promote the growth of NIH3T3 cells into which the CCK-B/gastrin receptor had been introduced via a eukaryotic expression vector. In this study, we have examined the effect of CCK-8 on the actin cytoskeleton by using two mouse fibroblast cell lines expressing human CCK-B/gastrin receptors. Treatment with very low concentration of CCK-8 (10(-10) M) induced the formation of actin stress fibers within one minute. Stress fiber formation increased for 30 min. In contrast, a potent mitogen for fibroblasts, platelet-derived growth factor (PDGF), initially induced membrane ruffling and, later, a weak formation of stress fibers. Microinjection of rho GDP dissociation inhibitor or Clostridium botulinum ADP-ribosyltransferase C3 which is known to impair the function of a small GTP-binding protein, rho p21, inhibited the stress fiber formation by CCK-8 as well as by PDGF. These results indicate that CCK-B/gastrin receptor could regulate stress fiber formation in a rho p21-dependent manner. The signals from CCK-B/gastrin receptor might affect cell growth as well as cell motility or adhesion by regulating the actin cytoskeleton.
Taniguchi
T
T
Department of Medicine, Kobe University School of Medicine, Japan.
Takaishi
K
K
Murayama
T
T
Ito
M
M
Iwata
N
N
Chihara
K
K
Sasaki
T
T
Takai
Y
Y
Matsui
T
T
D016475:3T3 Cells / Q000378:metabolism* / Q000648:ultrastructure; D036002:ADP Ribose Transferases / Q000494:pharmacology; D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D001905:Botulinum Toxins; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D051379:Mice; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D000199:Actins; D020730:Guanine Nucleotide Dissociation Inhibitors; D011949:Receptors, Cholecystokinin; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D012844:Sincalide