EGFR family-mediated signal transduction in the human keratinocyte cell line HaCaT

We analyzed the formation of homo- and heterodimers between EGFR, ErbB2, an d ErbB3 (members of the EGF receptor family) in the human skin keratinocyte cell Line HaCaT, in dependence of the added ligand. ErbB4 was not unambigu ously identified. By immunoprecipitation and Western blots, we showed the f ormation of heterodimers between all members of the family. Whereas EGF and TGF-alpha strongly induced heterodimerization, no effect was observed with heregulin. At the concentrations used all ligands elicited a similar, diff erentiation-independent activation of erk1/2 MAP kinase, with the exception of heregulin which activated p42/44 only marginally. We also found that di fferent ligands triggered different transcription patterns of "early genes, " with the exception of heregulin which did not, modulate transcription. TG F-alpha was the most efficient Ligand in promoting incorporation of tritiat ed thymidine into the DNA. (C) 1999 Academic Press.