Trafficking of the ErbB Receptors and its Influence on Signaling

Journal Article · Mon Mar 10 04:00:00 EST 2003 · Experimental Cell Research, 284(1):78-88

DOI:https://doi.org/10.1016/S0014-4827(03)00002-8· OSTI ID:15004326

Wiley, H Steven ^[1]

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1. BATTELLE (PACIFIC NW LAB)

Although members of the ErbB receptor family are found predominantly at the cell surface, these receptors undergo constant cycling between the plasma membrane and the endosomal compartment. In the absence of an activating ligand, these receptors are slowly internalized (t1/2~ 30 min), but are quickly recycled. The constitutive degradation rate of the EGF receptor (EGFR) is slower than other ErbB family members and only the EGFR appears to alter its trafficking pattern in response to ligand binding. This altered pattern is characterized by accelerated internalization and enhanced lysosomal targeting. Ligand-regulated trafficking of the EGFR is mediated by a series of motifs distributed through the cytoplasmic domain of the receptor that are exposed by a combination of activation-mediated conformation changes and the binding of proteins, such as Grb2. As a consequence of induced internalization, most EGFR signaling occurs within endosomes whereas signaling by the other members of the ErbB family appear to be generated predominantly from the cell surface. Overexpression of ErbB family members can disrupt normal receptor trafficking by driving heterodimerization of receptors with disparate trafficking patterns. Because different ErbB receptor substrates are localized in different cellular compartments, disrupted trafficking could be an important factor is the altered signaling patterns observed as a consequence of receptor overexpression.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC06-76RL01830
• OSTI ID: 15004326
• Report Number(s): PNWD-SA-5888
• Journal Information: Experimental Cell Research, 284(1):78-88, Journal Name: Experimental Cell Research, 284(1):78-88 Journal Issue: 1 Vol. 284; ISSN 0014-4827; ISSN 1090-2422
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
COMPARTMENTS
MEMBRANES
PLASMA
PROTEINS
SUBSTRATES
cancer
receptors
signaling
trafficking