ErbB-3 mediates differential mitogenic effects of NDF/heregulin isoforms on mouse keratinocytes.

摘要: The family of Neu differentiation factors (NDFs, or heregulins) includes a dozen secreted glycoproteins, whose receptor binding domain displays two variants, alpha and beta, they bind to tyrosine kinases, ErbB-3 ErbB-4. Certain isoforms were reported induce growth-arrest mammary tumor cells, while other breast cancer cell lines responded mitogenically. present study addressed the biologic effects various NDF on normal EGF-dependent epithelial Balb/MK keratinocytes, that can undergo either proliferation differentiation. We found beta induced mitogenic effect, was significantly smaller than maximal response EGF. By contrast with NDF-beta, NDF-alpha exerted almost no but sufficient maintain keratinocytes in culture. Consistent their higher potency, NDF-beta bound cells affinity (Kd = 2.2 nM) isoforms, however both groups shared receptor, we identified as ErbB-3. No transcript ErbB-4 detectable these express multiple mRNAs also ErbB-2. conclude different distinct growth regulatory cultured through direct interaction