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2011-07-08

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177307

Transautocrine signaling by membrane neuregulins requires cell surface targeting, which is controlled by multiple domains

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https://doi.org/10.1074/jbc.M110.190835

Resum

The neuregulins (NRGs) play important roles in animal development and homeostasis, and their deregulation has been linked to diseases such as cancer and schizophrenia. The NRGs belong to the epidermal growth factor (EGF) family of transmembrane growth factors. Although NRGs may be synthesized as transmembrane proteins (the pro-NRGs), some of them lack an N-terminal signal sequence, raising the question of how these pro-NRGs are directed to the plasma membrane. Here we have explored the domains of pro-NRGs that are required for their membrane anchoring, cell surface exposure, and biological activity. We show that an internal hydrophobic region acts as a membrane-anchoring domain, but other regions of pro-NRG are required for proper sorting to the plasma membrane. Using mutants that are located in different subcellular compartments, we show that only plasma membrane-exposed pro-NRG is biologically active. At this location, the pro-NRGs may act as transautocrine molecules (i.e. as membrane factors able to activate receptors present in cells that are in physical contact with the pro-NRG-producing cells (in trans) or capable of activating receptors present in the pro-NRG-producing cells (in cis)).

Matèries

Membranes cel·lulars, Proteïnes de membrana, Transducció de senyal cel·lular, Metabolisme, Fisiologia

Matèries (anglès)

Cell membranes, Membrane proteins, Cellular signal transduction, Metabolism, Physiology

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Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

MONTERO, Juan carlos, RODRIGUEZ BARRUECO, Ruth, PANDIELLA, Atanasio. Transautocrine signaling by membrane neuregulins requires cell surface targeting, which is controlled by multiple domains. _Journal of Biological Chemistry_. 2011. Vol. 286, núm. 27, pàgs. 24350-24363. [consulta: 2 de febrer de 2026]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/177307]

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