Differential effects of amphiregulin and TGF-alpha on the morphology of MDCK cells.
Although both amphiregulin and TGF-alpha are known to exert their effects through the EGF receptor, we find that concentrations of recombinant human amphiregulin and TGF-alpha that are equipotent in EGF receptor activation and mitogenesis exhibit markedly different effects on MDCK cell morphology. Amphiregulin induces a spindle-like morphology that is associated with a redistribution of E-cadherin from a Triton-insoluble to Triton-soluble pool. TGF-alpha does not affect epithelial morphology nor does it affect the distribution of the Triton-soluble or -insoluble pool of E-cadherin. The effects of amphiregulin on E-cadherin are associated with actin rearrangement. The morphological and biochemical effects of amphiregulin are prevented by EGF receptor blockade but require Src-family kinase activity and MAPK signaling. These results identify an action of amphiregulin that is distinct from TGF-alpha that may contribute to amphiregulin's participation in the pathogenesis of inflammatory disorders like psoriasis and cancer.
Chung
Eunkyung
E
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2279, USA.
Graves-Deal
Ramona
R
Franklin
Jeffrey L
JL
Coffey
Robert J
RJ
D066258:Amphiregulin; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D004285:Dogs; D066255:EGF Family of Proteins; D066246:ErbB Receptors / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors