HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A corrigendum has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in AJP - GI Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Scheving, L. A. Articles by Russell, W. E. Search for Related Content PubMed PubMed Citation Articles by Scheving, L. A. Articles by Russell, W. E.

LIVER AND BILIARY TRACT

The emergence of ErbB2 expression in cultured rat hepatocytes correlates with enhanced and diversified EGF-mediated signaling

¹Division of Endocrinology, Department of Pediatrics, ²Department of Cell and Developmental Biology, ³Digestive Disease Research Center, ⁴Vanderbilt Diabetes Center, and ⁵Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee

Submitted 18 July 2005 ; accepted in final form 15 March 2006

The proliferative effects of EGF in liver have been extensively investigated in cultured hepatocytes. We studied the effects of EGF, insulin, and other growth regulators on the expression, interaction, and signaling of ErbB receptors in primary cultures of adult rat hepatocytes. Using immunological methods and ErbB tyrosine kinase inhibitors, we analyzed the expression and signaling patterns of the ErbB kinases over 120 h of culture. Basal and EGF-stimulated protein tyrosine phosphorylation increased as cells adapted in vitro. EGF receptor (EGFr) expression declined in the first 24 h, whereas ErbB3 expression rose. Although ErbB2 was not present in freshly isolated hepatocytes, EGF and insulin independently induced ErbB2 while suppressing ErbB3 expression. Low concentrations of EGF and insulin synergistically stimulated ErbB2 expression and DNA synthesis. The greatest increase in ErbB2, which is normally expressed by fetal and neonatal hepatocytes, occurred shortly before the onset of DNA synthesis (>40 h). EGF promoted EGFr and ErbB2 coassociation, stimulating tyrosine phosphorylation of both proteins. In contrast, heregulin ₁ (HRG-₁) did not promote ErbB2 and ErbB3 coassociation. A selective tyrphostin inhibitor of ErbB2 suppressed EGF-stimulated DNA synthesis, but maximum suppression required the blockade of the EGFr kinase as well. Maximal EGF stimulation of DNA synthesis in vitro depends on the induction of ErbB2 and involves an EGFr-ErbB2 heterodimer. The ability of insulin to induce ErbB2 suggests both a mechanism for the synergy between insulin and EGF and a possible metabolic control of ErbB2 in vivo.

hepatocyte; liver; TGF-; cell culture

Related articles in AJP - GI:

Corrigendum

AJP - GI 2006 291: G751. [Full Text]  

This article has been cited by other articles:

				L. A. Scheving, M. C. Stevenson, X. Zhang, and W. E. Russell Cultured rat hepatocytes upregulate Akt and ERK in an ErbB-2-dependent manner Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G322 - G331. [Abstract] [Full Text] [PDF]

				L. A. Scheving, R. Buchanan, M. A. Krause, X. Zhang, M. C. Stevenson, and W. E. Russell Dexamethasone modulates ErbB tyrosine kinase expression and signaling through multiple and redundant mechanisms in cultured rat hepatocytes Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G552 - G559. [Abstract] [Full Text] [PDF]