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Oncogene ERBB4 (HER4) is a member of the type I receptor protein tyrosine subfamily that includes EGFR, ERBB2, and ERBB3. ERBB4 binds and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. ErbB 4 is activated by neuregulins and NTAK (neural and thymus derived activator for ErbB kinases). ErbB 4 is a receptor for heregulin and is capable of mediating HGL-stimulated tyrosine phosphorylation of itself. Like other protein kinases, ErbB 4 mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. ErbB 4 is most predominantly expressed in several breast carcinoma cell lines, and in normal skeletal muscle, heart, pituitary, brain, and cerebellum. Breast tumor cell lines T47-D, MDA-MB-453, BT-474 and H3396 are found to have the highest levels of mRNA, and intermediate levels are seen in MCF-7, MDAMB-330 and MDA-MB-361. Expression of ErbB 4 is low or absent in some breast tumor cell lines such as MDA-MB-231, MDA-MB-157, MDA-MB-468, and SKBR-3. ErbB 4 levels have been found to be elevated in certain human tumor cell lines suggesting that it may play a role in some malignancies.
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