Related Experiment Videos
Identification of the ron gene product as the receptor for the human macrophage stimulating protein
M H Wang1, C Ronsin, M C Gesnel
1Immunopathology Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.
Abstract:
Macrophage-stimulating protein (MSP) is a member of the hepatocyte growth factor-scatter factor (HGF-SF) family. Labeled MSP bound to Madin-Darby canine kidney (MDCK) cells transfected with complementary DNA encoding Ron, a cell membrane protein tyrosine kinase. Cross-linking of 125I-labeled MSP to transfected cells (MDCK-RE7 cells) and immunoprecipitation by antibodies to Ron revealed a 220-kilodalton complex, a size consistent with that of MSP (80 kilodaltons) cross-linked to the beta chain of Ron (150 kilodaltons). The binding of 125I-labeled MSP to MDCK-RE7 cells was inhibited by unlabeled MSP, but not by HGF-SF. MSP caused phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells. These results establish the ron gene product as a specific cell-surface receptor for MSP.
Insights
Macrophage-stimulating protein (MSP) specifically binds to the Ron receptor tyrosine kinase. This binding triggers cellular responses, confirming Ron as MSP's cell-surface receptor.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Macrophage-stimulating protein (MSP) belongs to the hepatocyte growth factor-scatter factor (HGF-SF) family.
- Understanding MSP's cellular interactions is crucial for deciphering its biological functions.
Purpose of the Study:
- To identify and characterize the specific cell-surface receptor for Macrophage-stimulating protein (MSP).
- To investigate the functional consequences of MSP binding to its receptor.
Main Methods:
- Utilized Madin-Darby canine kidney (MDCK) cells transfected with the Ron complementary DNA.
- Employed cross-linking and immunoprecipitation techniques with 125I-labeled MSP and anti-Ron antibodies.
- Assessed MSP binding specificity and its effect on Ron phosphorylation and cell migration.
Main Results:
- Identified a 220-kilodalton complex formed by MSP (80 kDa) and the beta chain of Ron (150 kDa).
- Demonstrated that MSP binding to MDCK-RE7 cells is specific and inhibited by unlabeled MSP, but not HGF-SF.
- Observed MSP-induced phosphorylation of the Ron beta chain and subsequent migration of MDCK-RE7 cells.
Conclusions:
- The gene product Ron functions as the specific cell-surface receptor for Macrophage-stimulating protein (MSP).
- MSP binding to Ron initiates downstream signaling pathways, including receptor phosphorylation and cell migration.