Alterations in the cAMP signal transduction pathway in mouse lung tumorigenesis

Carol A. Lange-Carter, Alvin M. Malkinson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Alterations in the cAMP signal transduction pathway are associated with mouse lung neoplasia. cAMP effects are mediated by activating cAMP-dependent protein kinase isozymes, PKA I and PKA II. E9, a tumorigenic cell line, exhibited decreased PKA I levels compared to C10 cells, a nontumorigenic cell line of similar epithelial origin. Western immunoblots of PKA subunit proteins demonstrated low concentrations of both the catalytic (C) and regulatory (RI) PKA I subunits. Although RII (regulatory subunit of PKA II) concentrations were similar in both cell lines, RII from E9 cells was more highly phosphorylated than in C10 cells. RII phosphorylation status regulates cAMP activation of PKA II. Northern-blot analysis of mRNA content indicated diminished expression of both C and RI mRNA in E9 relative to C10 cells. Several endogenous PKA substrate proteins present in C10 cells were minimally phosphorylated by PKA in E9 cells. Forskolin, which raises cellular cAMP content, increased phosphorylation of a protein doublet in intact C10 cells, but not in E9 cells. Decreased PKA I expression and alterations in RII phosphorylation in lung neoplasia may contribute to anomalous regulation by cAMPI thereby diminishing cAMP-mediated growth inhibitory effects.

Original languageEnglish (US)
Pages (from-to)341-357
Number of pages17
JournalExperimental Lung Research
Volume17
Issue number2
DOIs
StatePublished - 1991
Externally publishedYes

Bibliographical note

Funding Information:
We gratefully acknowledge Susan D. Jennings for excellent technical assistance and Dr. John M. Shannon (National Jewish Center for Immunology and Respiratory Medicine, Denver) for generous use of his laboratory facilities and advice concerning molecular biology techniques. This work was supported by USPHS grant ES02370.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Fingerprint Dive into the research topics of 'Alterations in the cAMP signal transduction pathway in mouse lung tumorigenesis'. Together they form a unique fingerprint.

Cite this