Receptor occupation, calcium mobilization, and amylase release in pancreatic acini: effect of CCK-JMV-180

Sato, Shigeo; Stark, Howard A.; Martínez, José Luis Lázaro; Beaven, Michael A.; Jensen, Robert T.; Gardner, Jerry D.

doi:10.1152/ajpgi.1989.257.2.g202

Cited by 40 publications

(66 citation statements)

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“…CCK-JMV antagonized the ability of CCK-8 to stimulate tyrosine phosphorylation of all six phosphospecific sites. This result confirmed that activation of the low affinity CCK A receptor state, for which CCK-JMV is an antagonist (31,33), is also involved in the ability of CCK to cause maximal stimulation of tyrosine phosphorylation at each site in each kinase. With the use of CCK-JMV, we could demonstrate that in the case of the PYK2 phosphospecific sites, ϳ45% of the phosphorylation was mediated by the high affinity state, whereas in the case of the three FAK phosphospecific sites, less than 20% of the phosphorylation was mediated by the high affinity state.…”

Section: Resultssupporting

confidence: 75%

“…Our results support the conclusion that CCK is stimulating tyrosine phosphorylation at each of the three FAK-and PYK2-specific sites by activation of both receptor states; however, the extent of participation by each state varies with the different specific phosphorylation site. This conclusion is supported by the finding that CCK-JMV, which functions as an agonist at the high affinity receptor state and as an antagonist on the low affinity receptor state in rat pancreatic acini (31)(32)(33), stimulated tyrosine phosphorylation at each of the three sites in each kinase, demonstrating that stimulation of the CCK A receptor high affinity state participates in phosphorylation at each of three sites in both kinases. However, CCK-JMV did not stimulate to the same maximal extent as CCK, suggesting that activation of the high affinity state of the CCK A receptor only accounted for some of the stimulation caused by CCK.…”

Section: Resultsmentioning

confidence: 68%

“…Numerous studies show that CCK A can activate both a high and low affinity state and can mediate different cellular responses (20,30,31). To establish the degree of participation of the high and low CCK A receptor states in tyrosine phosphorylation of each PYK2 and FAK phosphospecific site, we treated pancreatic acini with CCK-JMV (1 M), which is known to be an agonist at the CCK A high affinity receptor state and an antagonist at the low affinity CCK A receptor state in rat pancreatic acini (31)(32)(33).…”

Section: Resultsmentioning

confidence: 99%

“…To establish the degree of participation of the high and low CCK A receptor states in tyrosine phosphorylation of each PYK2 and FAK phosphospecific site, we treated pancreatic acini with CCK-JMV (1 M), which is known to be an agonist at the CCK A high affinity receptor state and an antagonist at the low affinity CCK A receptor state in rat pancreatic acini (31)(32)(33). At all six phosphospecific sites a 1 M concentration of CCK-JMV, which is known to be maximally effective as an agonist for the high affinity and as an antagonist for the low affinity CCK A receptor state (31)(32)(33), stimulated tyrosine phosphorylation from 9 to 45% of the maximum response seen with CCK-8 (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…1 The abbreviations used are: FAK, p125 FAK (p125 FAK focal adhesion kinase); PYK2, proline-rich kinase 2 (cell adhesion kinase ␤); CCK, cholecystokinin; CCK A receptor, cholecystokinin receptor type A; PKC, protein kinase C; CCK-JMV, [Nle 28,31 ]-2-phenylethylester; PLC, phospholipase C; pAb, polyclonal antibody; mAb, monoclonal antibody; HUVEC, human umbilical vein endothelial cells.…”

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confidence: 99%

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Phosphospecific Site Tyrosine Phosphorylation of p125FAK and Proline-rich Kinase 2 Is Differentially Regulated by Cholecystokinin Receptor Type A Activation in Pancreatic Acini

Pace

García‐Marín

Tapia

et al. 2003

Journal of Biological Chemistry

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The focal adhesion kinases, p125 FAK and proline-rich kinase 2 (PYK2), are involved in numerous processes as adhesion, cytoskeletal changes, and growth. These kinases have 45% homology and share three tyrosine phosphorylation (TyrP) sites. Little information exists on the ability of stimulants to cause TyrP of each kinase site and the cellular mechanism involved. We explored the ability of the neurotransmitter/hormone, CCK, to stimulate TyrP at each site. In rat pancreatic acini, CCK stimulated TyrP at each site in both kinases. TyrP was rapid except for pY397FAK. The magnitude of TyrP differed with the different FAK and PYK2 sites. The CCK dose-response curve for TyrP for sites in each kinase was similar. CCK-JMV, an agonist of the high affinity receptor state and antagonist of the low affinity receptor state, was less efficacious than CCK at each FAK/ PYK2 site and inhibited CCK maximal stimulation. Thapsigargin decreased CCK-stimulated TyrP of pY402PYK2 and pY925FAK but not the other sites. GF109203X reduced TyrP of only the PYK2 sites, pY402 and pY580. GF109203X with thapsigargin decreased TyrP of pY402PYK2 and the three FAK sites more than either inhibitor alone. Basal TyrP of pY397FAK was greater than other sites. These results demonstrate that CCK stimulates tyrosine phosphorylation of each of the three homologous phosphorylation sites in FAK and PYK2. However, CCK-stimulated TyrP at these sites differs in kinetics, magnitude, and participation of the high/low affinity receptor states and by protein kinase C and [Ca 2؉ ] i . These results show that phosphorylation of these different sites is differentially regulated and involves different intracellular mechanisms in the same cell.The closely related nonreceptor focal adhesion tyrosine kinases (FAK) 1 p125 FAK and PYK2 transduce key extracellular signals that are involved in mediating growth, adhesion, cytoskeletal changes, and cellular motility (1-3). These kinases are activated by such diverse stimuli as integrins, some G protein-coupled receptors, growth factors, bioactive lipids, oncogenes (2, 4 -7), and mechanical factors (pressure, stretch, and shock) (2, 8 -10). PYK2 and FAK share 45% overall sequence homology and undergo tyrosine phosphorylation at related sites (1-3, 11). During activation FAK tyrosine phosphorylation occurs at six or more sites in vivo (11). Two sites are located within the N-terminal domain (pY397 and pY407), two sites are within the kinase activation loop (pY576 and pY577), and two sites are within the C-terminal domain (pY861 and pY925). The pY397FAK site serves as an autophosphorylation site (11) and once phosphorylated as a binding site for c-Src family protein tyrosine kinases (12, 13) and other proteins such as phosphatidylinositol 3-kinase (14) and phospholipase C␥ (15). The phosphorylation of pY576 and pY577 in the kinase activation loop is essential for full catalytic activity (11). Phosphorylation of pY925 FAK in the C-terminal domain is followed by binding of SH-2 domain containing proteins such as Grb2 (16). The role...

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Section: Resultssupporting

confidence: 75%

Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Phosphospecific Site Tyrosine Phosphorylation of p125FAK and Proline-rich Kinase 2 Is Differentially Regulated by Cholecystokinin Receptor Type A Activation in Pancreatic Acini

Pace

García‐Marín

Tapia

et al. 2003

Journal of Biological Chemistry

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PRDM14 is overexpressed in chronic pancreatitis prior to pancreatic cancer

2018

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Pancreatic ductal adenocarcinoma ( PDAC ) is an aggressive and lethal cancer that is typically diagnosed at a later stage with metastases and is difficult to treat. Therefore, investigating the mechanism of PDAC initiation is important to aid early‐stage cancer detection. PRDM 14 is a transcription factor that maintains pluripotency in embryonic stem cells and is overexpressed in several cancers. We previously reported that PRDM 14 is overexpressed and regulates cancer stem‐like phenotypes in PDAC , and herein, we assess whether PRDM 14 expression increases prior to tumorigenesis. Through immunohistochemistry analyses of clinical tissues, we detected PRDM 14‐positive cells in precursor pancreatic intraepithelial neoplasia and chronic pancreatitis, which is a risk factor for PDAC , lesions. PRDM 14 staining in chronic pancreatitis was as high as that in PDAC and cancer adjacent tissues. We induced pancreatitis in mouse models by cerulein injection, and observed that PRDM 14 expression increased in chronic pancreatitis models but not in control or acute pancreatitis mice. Moreover, cerulein treatment increased PRDM 14 expression in PK ‐1 and As PC ‐1 pancreatic cancer cell lines. Our results suggest that inflammation increases the expression of PRDM 14, which regulates cancer stem‐like phenotypes, and this occurs prior to PDAC initiation and progression.

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Regulation of gap junctional coupling in isolated pancreatic acinar cell pairs by cholecystokinin-octapeptide, vasoactive intestinal peptide (VIP) and a VIP-antagonist

Ngezahayo

Kolb

1994

J. Membarin Biol.

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Cholecystokinin-octapeptide (CCK-OP) induces a time- and dose-dependent decrease of gap junctional conductance in isolated pairs of pancreatic acinar cells. In double whole-cell experiments, the time course could be described by the latency and the half-life time (t1/2) of cell-to-cell uncoupling. The latency shows a biphasic dependence on [CCK-OP] with a minimum of about 50 sec at 10(-9) M CCK-OP. In the presence of vasoactive intestinal peptide (VIP), the biphasic relationship is shifted to lower CCK-OP concentrations. The increase of latency at high concentrations of CCK-OP (> 10(-9) M) was blocked by addition of a VIP-antagonist. t1/2 decreases monophasically with increasing [CCK-OP]. Addition of GTP gamma S to the pipette solution suppresses the [CCK-OP] dependence of the latency and potentiates the uncoupling phase. The kinetic data are discussed in terms of CCK binding to receptors of high and low affinity. Evidence is presented that secretion and cell-to-cell coupling are not related by an all-or-none process, but that for physiological CCK-OP concentrations, gap junctional uncoupling follows secretion.

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Receptor occupation, calcium mobilization, and amylase release in pancreatic acini: effect of CCK-JMV-180

Cited by 40 publications

References 0 publications

Phosphospecific Site Tyrosine Phosphorylation of p125FAK and Proline-rich Kinase 2 Is Differentially Regulated by Cholecystokinin Receptor Type A Activation in Pancreatic Acini

Phosphospecific Site Tyrosine Phosphorylation of p125FAK and Proline-rich Kinase 2 Is Differentially Regulated by Cholecystokinin Receptor Type A Activation in Pancreatic Acini

PRDM14 is overexpressed in chronic pancreatitis prior to pancreatic cancer

Regulation of gap junctional coupling in isolated pancreatic acinar cell pairs by cholecystokinin-octapeptide, vasoactive intestinal peptide (VIP) and a VIP-antagonist

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