Src-family Tyrosine Kinases in Activation of ERK-1 and p85/p110-phosphatidylinositol 3-Kinase by G/CCKBReceptors

Daulhac, Laurence; Kowalski‐Chauvel, Aline; Pradayrol, Lucien; Vaysse, Nicole; Seva, Catherine

doi:10.1074/jbc.274.29.20657

Cited by 104 publications

(88 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mitogen-activated protein kinases, ERK1/2, Jun kinase, and p38 MAPK, as well as phosphatidylinositol 3-kinase, are known targets of gastrin. Several groups, including ours, have documented the contribution of upstream Src and Fak family tyrosine kinases in the activation of these pathways (3)(4)(5)(6).…”

mentioning

confidence: 99%

Essential Interaction of Egr-1 at an Islet-specific Response Element for Basal and Gastrin-dependent Glucagon Gene Transactivation in Pancreatic α-Cells

Leung–Theung–Long

Roulet

Clerc

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The peptide hormone gastrin is secreted from G cells of the gastric antrum and is the main inducer of gastric acid secretion via activation of its receptor the cholecystokinin 2 (CCK2) receptor. Both gastrin and CCK2 receptors are also transiently detected in the fetal pancreas and believed to exert growth/differentiation effects during endocrine pancreatic development. We demonstrated previously that whereas gastrin expression is extinguished in adult pancreas, CCK2 receptors are present in human glucagon-producing cells where their activation stimulates glucagon secretion. Based on these findings, we investigate in the present study whether gastrin regulates glucagon gene expression. To this aim, the CCK2 receptor was stably expressed into a glucagon-producing pancreatic islet cell line, and a glucagon-reporter fusion gene was transiently transfected in this new cellular model. We report that gastrin stimulates glucagon gene expression in glucagon-producing pancreatic cells. By using progressively 5-increased sequences of the glucagon gene, gastrin responsiveness was located within the minimal promoter. Moreover, we clearly identified early growth response protein 1 (Egr-1) as an essential transcription factor interacting with the islet cell-specific G4 element. Egr-1 was shown to be essential for basal and gastrin-dependent glucagon gene transactivation. Furthermore, our results demonstrate that the MEK1/ERK1/2 pathway couples the CCK2 receptor to nuclearization and DNA binding of Egr-1. In conclusion, our data provide new information concerning the transcriptional regulation of the glucagon gene. Moreover they open new working hypothesis with reference to a potential role of gastrin in glucagon-producing pancreatic cells.

show abstract

mentioning

confidence: 99%

Essential Interaction of Egr-1 at an Islet-specific Response Element for Basal and Gastrin-dependent Glucagon Gene Transactivation in Pancreatic α-Cells

Leung–Theung–Long

Roulet

Clerc

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…3 Mitogen-activated protein kinases, ERK1/2, Jun kinase and p38MAPK, as well as the phosphatidylinositol 3-kinase (PI3K) and early responsive genes (c-fos, c-myc and c-jun), are known targets of gastrin. [4][5][6][7] Several groups including ours, have documented the contribution of Src and focal adhesion kinase (Fak) families' tyrosine kinases upstream the activation of these pathways. 4,8 The role of gastrin and CCK2 receptors as positive regulators of proliferation of normal gastrointestinal tissues is now well recognized.…”

mentioning

confidence: 99%

“…[4][5][6][7] Several groups including ours, have documented the contribution of Src and focal adhesion kinase (Fak) families' tyrosine kinases upstream the activation of these pathways. 4,8 The role of gastrin and CCK2 receptors as positive regulators of proliferation of normal gastrointestinal tissues is now well recognized. A number of reports have also suggested that amidated gastrin may be a growth factor for gastrointestinal cancers.…”

mentioning

confidence: 99%

Transgenic expression of CCK2 receptors sensitizes murine pancreatic acinar cells to carcinogen‐induced preneoplastic lesions formation

Mathieu

Clerc

Portolan

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

In humans, initial events of pancreatic carcinogenesis remain unknown, and the question of whether this cancer, which has a ductal phenotype, exclusively arises from duct cells has been raised. Previous studies have demonstrated that transgenic expression of the CCK2 receptor in acinar cells of ElasCCK2 mice plays a role in the development of pancreatic neoplasia. The aim of our study was to examine initial steps of carcinogenesis in ElasCCK2 mice, adding a supplementary defect by using a chemical carcinogen, azaserine. Results of posttreatment sequential immunohistochemical examinations and quantifications demonstrate that mice responded to azaserine. Transition of acinar cells into duct-like cells expressing Pdx1 and gastrin, as well as proliferation of acinar cells, were transiently observed in both transgenic and control mice. The carcinogen also induced formation of preneoplastic lesions, adenomas, exhibiting properties of autonomous growth. Importantly, expression of the CCK2 receptor increased the susceptibility of pancreas to azaserine. Indeed, treated ElasCCK2 mice exhibited larger areas of pancreatic acinar-ductal transition, increased cellular proliferation as well as larger adenomas areas vs. control mice. These amplified responses may be related to auto/paracrine stimulation of CCK2 receptor by gastrin expressed in newly formed duct-like cells. Our results demonstrate that activation of CCK2 receptor and azaserine result in cumulative effects to favor the emergence of a risk situation that is a potential site for initiation of carcinogenesis. ' 2005 Wiley-Liss, Inc.Key words: G protein coupled receptors; CCK2 receptor; precancerous conditions; gastrin; transdifferentiation; experimental animal model; developmental gene Peptides of the cholecystokinin (CCK)/gastrin family are present in the gastrointestinal tract where they are known to physiologically regulate gallbladder and bowel motility, pancreatic and gastric secretion as well as growth and trophicity of gastrointestinal epithelial mucosa. 1 Two receptors that mediate the actions of cholecystokinin and gastrin have been pharmacologically classified as CCK1 and CCK2 receptors on the basis of their binding affinity for their natural ligands. While the CCK1 receptor is highly selective towards cholecystokinin vs. gastrin, the CCK2 receptor binds the 2 agonists with similar high affinities. 2 Both are G-protein coupled receptors with extrinsic tyrosine kinase activity. They activate many intracellular mediators classically described in the regulation of mitogenesis by growth factors. 3 Mitogen-activated protein kinases, ERK1/2, Jun kinase and p38MAPK, as well as the phosphatidylinositol 3-kinase (PI3K) and early responsive genes (c-fos, c-myc and c-jun), are known targets of gastrin. 4-7 Several groups including ours, have documented the contribution of Src and focal adhesion kinase (Fak) families' tyrosine kinases upstream the activation of these pathways. 4,8 The role of gastrin and CCK2 receptors as positive regulators of proliferation of normal...

show abstract

“…Notably, volumesensitive tyrosine kinases have been shown to modulate the trafficking of epidermal growth factor receptors in liver cells (12); both insulin receptor and p60 c-src activities are closely associated with PI 3-kinase, which is known to regulate exoand endocytosis (11,33). To assess the possibility that membrane trafficking events may contribute to the NSC response, two complementary approaches were utilized.…”

Section: P60 C-src Represents a Candidate Volume-sensitive Tyrosine Kmentioning

confidence: 99%

Volume-sensitive Tyrosine Kinases Regulate Liver Cell Volume through Effects on Vesicular Trafficking and Membrane Na+ Permeability

Feranchak

Kilic

Wojtaszek

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

In liver cells, the influx of Na؉ mediated by nonselective cation (NSC) channels in the plasma membrane contributes importantly to regulation of cell volume. Under basal conditions, channels are closed; but both physiologic (e.g. insulin) and pathologic (e.g. oxidative stress) stimuli that are known to stimulate tyrosine kinases are associated with large increases in membrane Na ؉ permeability to ϳ80 pA/pF or more. Consequently, the purpose of these studies was to evaluate whether volumesensitive tyrosine kinases mediate cell volume increases through effects on the activity or distribution of NSC channel proteins. In HTC hepatoma cells, decreases in cell volume evoked by hypertonic exposure increased total cellular tyrosine kinase activity ϳ20-fold. Moreover, hypertonic exposure (320 -400 mosM) was followed after a delay by NSC channel activation and partial recovery of cell volume toward basal values (regulatory volume increase (RVI)). The tyrosine kinase inhibitors genistein and erbstatin prevented both NSC channel activation and RVI. Similarly, hypertonic exposure resulted in an increase in p60 c-src activity, and intracellular dialysis with recombinant p60 c-src led to activation of NSC currents in the absence of an osmolar gradient. Utilizing FM1-43 fluorescence, exposure to hypertonic media caused a rapid increase in the rate of exocytosis of ϳ40% (p < 0.01), and genistein inhibited both exocytosis and channel activation. These findings indicate that volume-sensitive increases in p60 c-src and/or related tyrosine kinases play a key role in the regulation of membrane Na ؉ permeability, suggesting that increases in the NSC conductance may be mediated in part through rapid recruitment of a distinct pool of channelcontaining vesicles.

show abstract

Src-family Tyrosine Kinases in Activation of ERK-1 and p85/p110-phosphatidylinositol 3-Kinase by G/CCKBReceptors

Cited by 104 publications

References 46 publications

Essential Interaction of Egr-1 at an Islet-specific Response Element for Basal and Gastrin-dependent Glucagon Gene Transactivation in Pancreatic α-Cells

Essential Interaction of Egr-1 at an Islet-specific Response Element for Basal and Gastrin-dependent Glucagon Gene Transactivation in Pancreatic α-Cells

Transgenic expression of CCK2 receptors sensitizes murine pancreatic acinar cells to carcinogen‐induced preneoplastic lesions formation

Volume-sensitive Tyrosine Kinases Regulate Liver Cell Volume through Effects on Vesicular Trafficking and Membrane Na+ Permeability

Contact Info

Product

Resources

About