Carbachol-stimulated Transactivation of Epidermal Growth Factor Receptor and Mitogen-activated Protein Kinase in T84 Cells Is Mediated by Intracellular Ca2+, PYK-2, and p60

Keely, Stephen J.; Calandrella, Sean; Barrett, Kim E.

doi:10.1074/jbc.275.17.12619

Cited by 136 publications

(127 citation statements)

References 53 publications

(57 reference statements)

Supporting

Mentioning

117

Contrasting

Order By: Relevance

“…4, B and D). Interestingly, Pyk2 and Src were implicated in promoting EGFR transactivation (4,38). The fact that these tyrosine phosphorylation pathways are upstream of ERK is further supported by our kinetic results demonstrating that the rapid activation of Pyk2 and Src preceded ERK activation (Fig.…”

Section: Discussionsupporting

confidence: 69%

Vasopressin-mediated mitogenic signaling in intestinal epithelial cells

Chiu

Santiskulvong

et al. 2002

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Here, we demonstrate that arginine vasopressin (AVP) induces multiple intracellular signal transduction pathways in rat intestinal epithelial IEC-18 cells via a V 1A receptor. Addition of AVP to these cells induces a rapid and transient increase in cytosolic Ca 2ϩ concentration and promotes protein kinase D (PKD) activation through a protein kinase C (PKC)-dependent pathway, as revealed by in vitro kinase assays and immunoblotting with an antibody that recognizes autophosphorylated PKD at Ser 916 . AVP also stimulates the tyrosine phosphorylation of the nonreceptor tyrosine kinase proline-rich tyrosine kinase 2 (Pyk2) and promotes Src family kinase phosphorylation at Tyr 418 , indicative of Src activation. AVP induces extracellular signal-related kinase (ERK)-1 (p44 mapk ) and ERK-2 (p42 mapk ) activation, a response prevented by treatment with mitogen-activated protein kinase kinase (MEK) inhibitors (PD-98059 and U-0126), specific PKC inhibitors (GF-I and Ro-31-8220), depletion of Ca 2ϩ (EGTA and thapsigargin), selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (tyrphostin AG-1478, compound 56), or the selective Src family kinase inhibitor PP-2. Furthermore, AVP acts as a potent growth factor for IEC-18 cells, inducing DNA synthesis and cell proliferation through ERK-, Ca 2ϩ -, PKC-, EGFR tyrosine kinase-, and Src-dependent pathways. arginine vasopressin; protein kinase D; protein kinase C; Src; proline-rich tyrosine kinase 2; intestinal epithelial proliferation THE SEQUENTIAL PROLIFERATION, lineage-specific differentiation, migration, and cell death of epithelial cells of the intestinal mucosa is a tightly regulated process that is modulated by a broad spectrum of regulatory peptides (8,36,70). The nontransformed IEC-6 and IEC-18 cells, derived from rat small intestinal crypt (56), have provided an in vitro model to examine intestinal epithelial cell migration, differentiation, and proliferation (16,27,58,70). Previous studies demonstrated that the proliferation and migration of these intestinal epithelial cells is regulated by a variety of polypeptide growth factors, including epidermal growth factor (EGF), insulin-like growth factor I, and hepatocyte growth factor, which act via single-pass transmembrane tyrosine kinase receptors (3,17,51). Neuropeptides and vasoactive peptides that signal through G protein-coupled receptors (GPCRs), characterized by seven-transmembrane helices, also act as potent cellular growth factors for a variety of cell types (63,64,66,67). However, the role of GPCRs and their ligands in intestinal epithelial cell signaling and proliferation remains poorly understood.The neurohypophysial nonapeptide arginine vasopressin (AVP), also known as antidiuretic hormone, is traditionally recognized for its role as a vasoconstrictor hormone acting on vascular smooth muscle cells and its antidiuretic effect via the renal collecting system. In addition to its function in the regulation of body fluid osmolality, vascular tone, and blood pressure, AVP acts as a growth-promo...

show abstract

Section: Discussionsupporting

confidence: 69%

Vasopressin-mediated mitogenic signaling in intestinal epithelial cells

Chiu

Santiskulvong

et al. 2002

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…7C). Calmodulin is a signaling molecule that mediates the effects of Ca 2ϩ mobilization in many systems (21). To test the role of Ca 2ϩ -mediated signaling on MIP-1␤ production, HMC-1 cells were pretreated with a calmodulin inhibitor fluphenazine before stimulation with fMLP.…”

Section: Role Of Extracellular Ca 2ϩ On Gpcr-induced Mip-1␤ Productiomentioning

confidence: 99%

Chemokine Production by G Protein-Coupled Receptor Activation in a Human Mast Cell Line: Roles of Extracellular Signal-Regulated Kinase and NFAT

Ali

Ahamed

Hernández-Munaín

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Chemoattractants are thought to be the first mediators generated at sites of bacterial infection. We hypothesized that signaling through G protein-coupled chemoattractant receptors may stimulate cytokine production. To test this hypothesis, a human mast cell line (HMC-1) that normally expresses receptors for complement components C3a and C5a at low levels was stably transfected to express physiologic levels of fMLP receptors. We found that fMLP, but not C3a or C5a, induced macrophage inflammatory protein (MIP)-1β (CCL4) and monocyte chemoattractant protein-1 (CCL2) mRNA and protein. Although fMLP stimulated both sustained Ca2+ mobilization and phosphorylation of extracellular signal-regulated kinase (ERK), these responses to C3a or C5a were transient. However, transient expression of C3a receptors in HMC-1 cells rendered the cells responsive to C3a for sustained Ca2+ mobilization and MIP-1β production. The fMLP-induced chemokine production was blocked by pertussis toxin, PD98059, and cyclosporin A, which respectively inhibit Giα activation, mitgen-activated protein kinase kinase-mediated ERK phosphorylation, and calcineurin-mediated activation of NFAT. Furthermore, fMLP, but not C5a, stimulated NFAT activation in HMC-1 cells. These data indicate that chemoattractant receptors induce chemokine production in HMC-1 cells with a selectivity that depends on the level of receptor expression, the length of their signaling time, and the synergistic interaction of multiple signaling pathways, including extracellular signal-regulated kinase phosphorylation, sustained Ca2+ mobilization and NFAT activation.

show abstract

“…In several studies, Gbg subunits (Luttrell et al, 1997b), increases in intracellular calcium (Keely et al, 1998;Zwick et al, 1997), cSrc activation (Keely et al, 2000;Luttrell et al, 1997b;Maudsley et al, 2000), and PYK2 activation (Keely et al, 2000) have all been shown to precede EGFR transactivation. In addition, the data showing that GPCR mediated HB ± EGF shedding can lead to ERK activation in nearby cells has raised questions about the spatial regulation of transactivation in situ.…”

Section: Receptor Tyrosine Kinase Transactivationmentioning

confidence: 99%