Src-mediated phosphorylation of RIAM promotes integrin activation
Frédéric Lagarrigue1, Alexandre R Gingras2
1Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Structure (London, England : 1993)
|April 2, 2021
Summary
Researchers discovered how RIAM protein movement is controlled. An interaction between two RIAM pleckstrin homology (PH) domains blocks a binding site, which is then reopened by Src phosphorylation, aiding integrin activation.
Area of Science:
- Biochemistry
- Cell Biology
- Structural Biology
Background:
- RIAM protein is crucial for integrin activation.
- RIAM's plasma membrane translocation is regulated by its pleckstrin homology (PH) domains.
- The precise mechanism of RIAM regulation remained unclear.
Purpose of the Study:
- To elucidate the structural basis of RIAM regulation.
- To understand how RIAM interacts with phosphoinositides.
- To explain the role of Src phosphorylation in RIAM function.
Main Methods:
- X-ray crystallography to determine the structure of RIAM PH domains.
- Biochemical assays to study phosphoinositide binding.
- In vitro phosphorylation assays using Src kinase.
Main Results:
- Identified an intermolecular interaction between two RIAM PH domains.
- Demonstrated that this interaction masks the phosphoinositide-binding site.
- Showed that Src-mediated phosphorylation unmasks the PH domain, enabling binding.
Conclusions:
- RIAM translocation is regulated by a novel PH domain interaction.
- Phosphorylation by Src is a key step in activating RIAM for integrin signaling.
- This finding provides a mechanistic link between RIAM structure and plasma membrane recruitment.
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