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The processes by which ErbB-3, an inactive tyrosine kinase, exerts its biological effects are poorly understood. Using the yeast two-hybrid system, we have isolated an ErbB-3 binding protein (Ebp1) that interacts with the juxtamembrane domain of ErbB-3. This protein is identical to that predicted to be encoded for by the human PA2G4 gene. Ebp1 is the human(More)
Ebp1, an ErbB-3 binding protein, translocates from the cytoplasm to the nucleus of human breast cancer cells after treatment with the ErbB-3 ligand, heregulin. The purpose of these studies was to examine the effects of ectopic expression of ebp1 on the biological properties of human ErbB-3-expressing breast carcinoma cell lines. Ectopic expression of ebp1(More)
The AU565 breast carcinoma cell line was used to determine the role of the extracellular-regulated kinase (ERK) pathway in mediating Heregulinbeta1 (HRGbeta1)-induced mammary cell differentiation. ERK activation remained elevated for 2 h following high doses of HRG which induce differentiation. In contrast, a transient 5 min peak of ERK activation in(More)
Several mutations in the tyrosine kinase domain of ErbB-3 have been postulated to render this enzyme catalytically inactive. To test which amino acid mutations in ErbB-3 might be critical for kinase inactivation, we used a yeast two hybrid assay of protein-protein interaction. We monitored restoration of ErbB-3 kinase activity by investigating the ability(More)
Specific biological responses to the erbB3-erbB4 ligand heregulin (HRG) have been postulated to be due to the formation of heterodimers of those receptors with erbB2. To test the role that erbB2 plays in the response to HRG in a human breast carcinoma cell line, antisense oriented erbB2 was stably transfected into AU565 cells. In the absence of HRG,(More)
Activation of phosphatidylinositol 3-kinase (PI-3K) has been shown to be critical for heregulin induced mitogenesis of human breast epithelial cells. However, the inhibitory effects of HRG have not been linked to PI3K activation. The purpose of these experiments was to determine the effects of heregulin beta 1 (HRG) on growth and PI3K activation of a(More)
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