Differential Signaling by the Epidermal Growth Factor-like Growth Factors Neuregulin-1 and Neuregulin-2

摘要: The neuregulins comprise a subfamily of epidermal growth factor (EGF)-like factors that elicit diverse cellular responses by activating members the ErbB family receptor tyrosine kinases. Although neuregulin-1 and neuregulin-2 are both binding ligands for ErbB3 ErbB4 receptors, they exhibit distinct biological activities depending on context. In MDA-MB-468 human mammary tumor cells, neuregulin-2beta (NRG2beta) inhibits cell growth, whereas neuregulin-1beta (NRG1beta) does not. these NRG2beta appears to preferentially act through EGF receptor, stimulating phosphorylation recruitment phospholipase C-gamma, Cbl, SHP2, Shc receptor. NRG1beta acts in cells phosphatidylinositol 3-kinase MDA-MB-453 stimulate ErbB2 receptors similar extents, but only potently stimulates morphological changes consistent with their differentiation. profiles SH2 domain-containing proteins efficiently recruited activated differ two factors. These observations indicate despite overlapping specificity, biochemical properties. Since lines express known our results imply EGF-like might differential signaling within context single heterodimer.