Crosstalk between epidermal growth factor receptor and P-glycoprotein in actinomycin D-resistant Chinese hamster lung cells Journal Article

  


Authors: Meyers, M. B.; Yu, P.; Mendelsohn, J.
Article Title: Crosstalk between epidermal growth factor receptor and P-glycoprotein in actinomycin D-resistant Chinese hamster lung cells
Abstract: Multidrug-resistant cells can manifest an increase in epidermal growth factor (EGF) receptor number along with increased P-glycoprotein (Pgp) synthesis. An interrelationship of the two membrane proteins in actinomycin D-resistant Chinese hamster lung cells (DC-3F/AD X) in terms of the effect of EGF on Pgp phosphorylation was investigated. EGF was not a mitogen for the resistant cells, nor was it mitogenic for DC-3F, the parental drug-sensitive line. Brief treatment of DC-3F/AD X cells with EGF resulted in a 30-50% decrease in the level of Pgp phosphorylation, and treatment of the cells with okadaic acid, a specific inhibitor of protein phosphatases-1 and -2A (PP1 and 2A), increased Pgp phosphorylation. Okadaic acid also increased phosphorylation of Pgp in plasma membranes isolated from DC-3F/AD X cells by 30-40%. Protein phosphatase activity in extracts of cells grown in EGF-containing medium was greater by 30% than that of cells grown in standard medium, and okadaic acid inhibited the increases. The results suggested that EGF activated PP1 and PP2A in DC-3F/AD X cells and that Pgp was a substrate for the phosphatases. The properties of Pgp may be modulated by the signalling system transduced by ligand-activated EGF receptor. © 1993.
Keywords: signal transduction; epidermal growth factor; controlled study; protein phosphorylation; nonhuman; cell proliferation; animal cell; animal; cell division; epidermal growth factor receptor; cell line; receptor, epidermal growth factor; drug resistance; enzyme inhibitor; phosphorylation; membrane glycoproteins; carrier proteins; cell membrane; dactinomycin; multidrug resistance; p-glycoprotein; phosphoprotein phosphatase; cricetulus; glycoprotein p; ethers, cyclic; okadaic acid; lung alveolus cell; priority journal; article; support, u.s. gov't, p.h.s.; hamsters; chinese hamster
Journal Title: Biochemical Pharmacology
Volume: 46
Issue: 10
ISSN: 0006-2952
Publisher: Elsevier Inc.  
Date Published: 1993-11-17
Start Page: 1841
End Page: 1848
Language: English
DOI: 10.1016/0006-2952(93)90591-j
PUBMED: 7902716
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027381585&doi=10.1016%2f0006-2952%2893%2990591-J&partnerID=40&md5=9090e173011dc6c57cf0630ecfd95a4f
Notes: Source: Scopus
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MSK Authors
  1. John Mendelsohn
    128 Mendelsohn
  2. Marian B. Meyers
    29 Meyers
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