High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor

Hempstead, Barbara L.; Martı́n-Zanca, Dionisio; Kaplan, David R.; Parada, Luis F.; Chao, Moses V.

doi:10.1038/350678a0

Cited by 1,139 publications

(532 citation statements)

References 79 publications

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“…TrkA was rapidly shown to mediate the known responses to NGF, such as neurite outgrowth and neuronal survival (Lee et al, 2001a;Lykissas et al, 2007), whereas the precise biological role of p75 NTR remained misunderstood. p75 NTR was shown to collaborate with TrkA to form high-affinity sites for NGF binding (Hempstead et al, 1991). In addition, p75 NTR was shown to alter the ligand specificity of other Trk receptors.…”

Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Dependence Receptors: a Short Historymentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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“…April 1992 Hempstead et al reported that the high-affinity receptor for nerve growth factor (NGF) requires formation of an heteromeric complex composed of the rrk tyrosine kinase proto-oncogene product and another molecule of low-affinity receptor for NGF [23]. Low affinity binding sites for HGF were present in both HGF-responsive epithelial cells and also in HGF-nonresponsive mesenchymal cells.…”

Section: Lettersmentioning

confidence: 99%

Expression of c‐met proto‐oncogene in COS cells induces the signal transducing high‐affinity receptor for hepatocyte growth factor

et al. 1992

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By transfection of the expression plasmid containing a human c-UTL'I cDNA into COS-7 cells, high-affinity binding sites specific for HGF with a Kd value of 30 pM were newly detected, Furthermore, only in the c-IIIPI transfected COS-7 cells, but not in the control COS-7cells, DNA synthesis was markedly induced in response to HGF. Thus, transient expression of exogenous C-III& cDNA resulted in the a;, lncarance of high-affinity receptor for HGF and conversion of the normally non-responsive COS-7 cells into the HGF-responsive cells. These results provide evidence for identifying the wtwt product as a signal transducing high-affinity receptor for HGF.

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“…The p75 gene, when transfected into nonneuronal cells, was shown to generate low a nity NGF binding sites, while expression in neuronal cells induced NGF-mediated cell di erentiation (Hempstead et al, 1989;Johnson et al, 1986;Matsushima and Bogenmann, 1990;Pleasure et al, 1990). Complex formation between p75 and trkA was observed, thus enhancing the NGF signal (Hempstead et al, 1991;Verdi et al, 1994). However, the p75 receptor belongs to the family of tumor necrosis factor receptors, and over expression in brain-derived cell lines induced apoptosis in the absence of NGF (Chao, 1992;Rabizadeh et al, 1993).…”

Section: Introductionmentioning

confidence: 99%