Vasopressin-mediated mitogenic signaling in intestinal epithelial cells |
| |
Authors: | Chiu Terence Wu Steven S Santiskulvong Chintda Tangkijvanich Pisit Yee Hal F Rozengurt Enrique |
| |
Affiliation: | Department of Medicine, School of Medicine, University of California-Los Angeles, 900 Veteran Ave., Los Angeles, CA 90095, USA. |
| |
Abstract: | The role of G protein-coupled receptorsand their ligands in intestinal epithelial cell signaling andproliferation is poorly understood. Here, we demonstrate that argininevasopressin (AVP) induces multiple intracellular signal transductionpathways in rat intestinal epithelial IEC-18 cells via aV1A receptor. Addition of AVP to these cells induces arapid and transient increase in cytosolic Ca2+concentration and promotes protein kinase D (PKD) activation through aprotein kinase C (PKC)-dependent pathway, as revealed by in vitrokinase assays and immunoblotting with an antibody that recognizesautophosphorylated PKD at Ser916. AVP also stimulates thetyrosine phosphorylation of the nonreceptor tyrosine kinaseproline-rich tyrosine kinase 2 (Pyk2) and promotes Src family kinasephosphorylation at Tyr418, indicative of Src activation.AVP induces extracellular signal-related kinase (ERK)-1(p44mapk) and ERK-2 (p42mapk) activation, aresponse prevented by treatment with mitogen-activated protein kinasekinase (MEK) inhibitors (PD-98059 and U-0126), specific PKC inhibitors(GF-I and Ro-31-8220), depletion of Ca2+ (EGTA andthapsigargin), selective epidermal growth factor receptor (EGFR)tyrosine kinase inhibitors (tyrphostin AG-1478, compound 56), or theselective Src family kinase inhibitor PP-2. Furthermore, AVP acts as apotent growth factor for IEC-18 cells, inducing DNA synthesis and cellproliferation through ERK-, Ca2+-, PKC-, EGFR tyrosinekinase-, and Src-dependent pathways. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《American journal of physiology. Cell physiology》浏览原始摘要信息 |
|
点击此处可从《American journal of physiology. Cell physiology》下载全文 |
|