Alternative pathways of epidermal growth factor receptor mediated contractile force in NR6 fibroblasts

Fred D. Allen, Clara F. Asnes, Alan Wells, Elliot L. Elson, Douglas A. Lauffenburger

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

We investigated the contractile force response to epidermal growth factor (EGF) stimulation in 3T3-derived NR6 fibroblast cells in order to determine significant pathways of biochemical signaling that mediate the response. We examined the force generating specificity of the EGF receptor (EGFR) signaling mechanism by using mutant NR6 fibroblasts expressing variations of the EGFR construct. The wild-type (WT) cell presented the complete internalizing EGFR signaling construct while the c'973 cell presented an internalization-defective EGFR construct, and the M721 cell presented a kinase-defective EGFR construct making it signaling inert. Additionally we examined the roles of the phospholipase C-γ (PLCγ) pathway by using the PLC inhibitor U73122 (1 μM) and the mitogen activated protein kinase (MAPK) pathway using the inhibitor PD98059 (10 μM) in the observed contractile force responses. We found that the WT cells showed a rapid but transient force increase within the first hour post-stimulation and the c'973 showed a more gradual increase in force which it sustained for several hours post-stimulation. Blocking the PLCγ activation in the WT cells reduced the peak force increase by 50% while blocking MAPK did not affect the force development in either WT or c'973 cells.

Original languageEnglish
Title of host publicationAmerican Society of Mechanical Engineers, Bioengineering Division (Publication) BED
PublisherASME
Pages113-114
Number of pages2
Volume43
ISBN (Print)0791816400
StatePublished - Dec 1 1999
EventAdvances in Bioengineering - 1999 (The ASME International Mechanical Engineering Congress and Exposition) - Nashville, TN, USA
Duration: Nov 14 1999Nov 19 1999

Conference

ConferenceAdvances in Bioengineering - 1999 (The ASME International Mechanical Engineering Congress and Exposition)
CityNashville, TN, USA
Period11/14/9911/19/99

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