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SH2-Bbeta is a Rac-binding protein that regulates cell motility
Maria Diakonova1, David R Gunter, James Herrington
1Department of Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0622, USA.
The Journal of Biological Chemistry
|January 12, 2002
Summary
SH2-Bbeta potentiates growth hormone-dependent cell motility by interacting with Rac. This adapter protein facilitates actin rearrangement and cell movement by recruiting Rac to activated growth factor receptors.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- SH2-Bbeta is a substrate for JAK2 tyrosine kinase and binds to activated growth factor receptors.
- SH2-Bbeta has been previously linked to growth hormone (GH) and platelet-derived growth factor (PDGF) regulation of the actin cytoskeleton.
Purpose of the Study:
- To investigate the role of SH2-Bbeta in GH-dependent cell motility.
- To identify the specific regions of SH2-Bbeta involved in potentiating GH-dependent cell movement.
Main Methods:
- Time-lapse video microscopy, phagokinetic assays, and wounding assays were used to assess cell motility.
- Co-immunoprecipitation experiments were performed to study protein-protein interactions.
- Dominant-negative mutants were employed to investigate the role of Rac in SH2-Bbeta-mediated effects.
Main Results:
- Overexpression of SH2-Bbeta mutants lacking an intact SH2 domain reduced cell movement.
- An N-terminal proline-rich domain (amino acids 85-106) of SH2-Bbeta is crucial for inhibiting motility in SH2 domain-deficient mutants.
- GH activates endogenous Rac, and SH2-Bbeta facilitates Rac recruitment to activated receptors, influencing actin rearrangement.
Conclusions:
- SH2-Bbeta acts as an adapter protein that enhances GH-dependent cell motility.
- The SH2 domain and an N-terminal proline-rich domain of SH2-Bbeta are critical for its function in regulating cell movement.
- SH2-Bbeta likely recruits Rac and other actin-regulating proteins to cytokine and growth factor receptors to facilitate actin rearrangement and cell motility.