Stem cell factor presentation to c-Kit. Identification of a basolateral targeting domain
1Department of Pathology, Centre Medical Universitaire, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland. Bernhard.Wehrle-Haller@medecine.unige.ch
The Journal of Biological Chemistry
|January 22, 2001
Summary
Stem cell factor requires a specific leucine-based signal for proper cell surface targeting. This mono-leucine determinant ensures correct protein localization and function, unlike mutations that cause endocytosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Stem cell factor (SCF), also known as mast cell growth factor or kit-ligand, is crucial for various biological processes.
- Proper cell surface expression of SCF is essential for its functions in pigmentation, fertility, learning, and hematopoiesis.
Purpose of the Study:
- To identify the specific signals within the cytoplasmic domain of SCF responsible for its basolateral membrane targeting.
- To elucidate the mechanism by which SCF maintains persistent cell surface expression.
Main Methods:
- Site-directed mutagenesis was employed to analyze the function of different regions within the SCF cytoplasmic domain.
- The study investigated the role of a mono-leucine determinant and adjacent acidic amino acids in protein sorting.
Main Results:
- A monomeric leucine-dependent basolateral targeting signal was identified in the SCF cytoplasmic domain.
- A cluster of acidic amino acids N-terminal to the leucine motif enhances basolateral sorting efficiency.
- The identified leucine motif does not induce endocytosis, allowing for sustained cell surface presence, unlike the Mgf(Sl17H) mutant.
Conclusions:
- Mono-leucine determinants represent a novel class of protein sorting signals for transmembrane growth factors.
- The findings provide insights into the regulation of SCF localization and its implications for biological functions.
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