Attenuation of EGF signaling in senescent cells by caveolin.
One of the characteristics of senescent cells is unresponsiveness to external stimuli like EGF. Although they have a normal level of receptors and downstream signaling molecules, EGF cannot induce the activation of Erk kinases and DNA synthesis in senescent cells as much as in young cells. Caveolin proteins directly interact with signaling molecules including EGF receptor and suppress the activation of EGFR upon EGF stimulation. We found that Erk activation after EGF stimulation in senescent human diploid fibroblasts was down-regulated. Those senescent cells showed an increased level of three isoforms of caveolin proteins. This change seems to lie in transcriptional control in senescent cells. We also demonstrated up-regulated caveolin proteins were co-localized with EGFR proteins in detergent-insoluble fractions. From these results, we suggest that the up-regulated expression of caveolin might explain the unresponsiveness of senescent fibroblasts to EGF stimulation.
Park
W Y
WY
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Korea.
Cho
K A
KA
Park
J S
JS
Kim
D I
DI
Park
S C
SC
D000818:Animals; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1; D051243:Caveolin 2; D051244:Caveolin 3; D022461:Caveolins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004171:Diploidy; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009928:Organ Specificity; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D014158:Transcription, Genetic
C495540:CAV1 protein, human; C495537:Cav1 protein, rat; C495549:Cav3 protein, rat; D051242:Caveolin 1; D051243:Caveolin 2; D051244:Caveolin 3; D022461:Caveolins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases