The ErbB2 receptor tyrosine kinase plays a critical role in a variety of developmental processes, and its aberrant activation may contribute to the progression of some breast and ovarian tumors. ASGP2, a transmembrane glycoprotein found on the surface of the highly metastatic ascites 13762 rat mammary adenocarcinoma cell line, is constitutively associated with ErbB2 in these cells and in mammary tissue from pregnant rats. Expression studies indicate that ASGP2 interacts directly and specifically with ErbB2 through one of its epidermal growth factor-like domains and that the co-expression of the two proteins in the same cell dramatically facilitates their direct stable interaction. Ectopic expression of ASGP2 in human melanoma tumor cells potentiates the response of endogenous ErbB2 to the neuregulin-1 growth factor. These observations point to a novel intramembrane mechanism for the modulation of receptor tyrosine kinase activity.ErbB2 (also known as Neu) is a 185-kDa cell surface transmembrane receptor tyrosine kinase that mediates the growth or differentiation of a variety of cultured cells and contributes to the proper development of cardiac and neural tissues during gestation (1-4). Its overexpression in numerous human tumors, including breast and ovarian tumors, correlates with earlier patient relapse and poor prognosis (5, 6). The observation that ErbB2 overexpression stimulates its protein-tyrosine kinase activity (7), together with the observation that activated alleles of the erbB2 gene induce metastatic tumors when expressed in murine mammary epithelium (8), suggest that the activation of ErbB2 kinase activity may play an important role in tumorigenesis or tumor progression.The protein-tyrosine kinase activity of ErbB2 may be activated by several soluble, diffusible ligands that possess epidermal growth factor (EGF) 1 -like domains. For example, EGF, transforming growth factor-␣, and amphiregulin are all capable of stimulating ErbB2 activity by binding to the related EGF receptor and promoting its heterodimerization with ErbB2 (9, 10). Likewise, the neuregulins (NRGs) bind to the ErbB3 and ErbB4 receptors and stimulate ErbB2 activity through receptor heterodimerization mechanisms (11,12). However, no molecularly characterized diffusible ligand has been demonstrated to act on ErbB2 directly, and it has been suggested that the primary function of this protein is to augment signaling through the ErbB receptor network by acting as an auxiliary co-receptor (13)(14)(15). In this context factors that influence the activity or availability of ErbB2 could have a significant impact on the strength or specificity of signaling and ultimately the cellular response. Strong candidates for such factors are cell surface proteins that possess EGF-like domains.The autonomously proliferating and highly metastatic rat ascites 13762 mammary adenocarcinoma cell line expresses a large sialomucin complex in abundance at its cell surface. This complex consists of two noncovalently associated proteins, ASGP1 and ASGP2, which ari...
EGFR, ErbB2 and ErbB3 are expressed by the ocular surface epithelia. EGFR is preferentially expressed by the basal epithelial cells that have the greatest proliferative potential. In contrast, ErbB2 and ErbB3 are preferentially expressed by the superficial differentiated ocular surface epithelia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.