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Updated: Aug 11, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
Published on: September 8, 2010
Biochemical analysis of the ligand for the neu oncogenic receptor
1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Abstract:
The neu protooncogene (also called HER2 and c-erbB2) encodes a cell-surface tyrosine kinase structurally related to the receptor for the epidermal growth factor (EGF). We have previously reported that a candidate ligand for the neu receptor is secreted by ras-transformed fibroblasts. Biochemical analyses of the neu stimulatory activity indicate that the ligand is a 35-kDa glycoprotein that is heat stable but sensitive to reduction. The factor is precipitable by either high salt concentrations or acidic alcohol. Partial purification of the molecule by selective precipitation, heparin-agarose chromatography, and gel filtration in dilute acid resulted in an active ligand, which is capable of stimulating the protooncogenic receptor but is ineffective on the oncogenic neu protein, which is constitutively active. The purified fraction, however, retained the ability to stimulate also the related receptor for EGF, suggesting that these two receptors are functionally coupled through a bidirectional mechanism. Alternatively, the presumed ligand interacts simultaneously with both receptors. The presented biochemical characteristics of the factor are expected to enable a completely purified factor with which to explore these possibilities.
Insights
Researchers identified a 35-kDa glycoprotein ligand that stimulates the neu receptor (HER2). This factor also activates the epidermal growth factor (EGF) receptor, suggesting functional coupling between these key signaling molecules.
Area of Science:
- Molecular Biology
- Cell Signaling
- Oncology
Background:
- The neu protooncogene (HER2/c-erbB2) encodes a cell-surface tyrosine kinase.
- It is structurally related to the epidermal growth factor (EGF) receptor.
- A candidate ligand for the neu receptor is secreted by ras-transformed fibroblasts.
Purpose of the Study:
- To biochemically characterize the neu receptor stimulatory factor.
- To investigate the functional relationship between the neu and EGF receptors.
Main Methods:
- Partial purification using selective precipitation, heparin-agarose chromatography, and gel filtration.
- Biochemical analyses of the ligand's properties (heat stability, sensitivity to reduction, precipitation).
- Assays to test the ligand's activity on protooncogenic neu and EGF receptors.
Main Results:
- The neu stimulatory factor is a 35-kDa glycoprotein, heat-stable but reduction-sensitive.
- The partially purified ligand stimulated the protooncogenic neu receptor but not the constitutively active oncogenic neu protein.
- The purified fraction also stimulated the EGF receptor, indicating potential functional coupling.
Conclusions:
- The identified glycoprotein ligand plays a role in neu receptor activation.
- Functional coupling or simultaneous interaction between neu and EGF receptors is suggested.
- Further purification is needed to fully elucidate the ligand's mechanism of action.
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