Journal
NATURE CELL BIOLOGY
Volume 13, Issue 11, Pages 1315-U77Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2340
Keywords
-
Categories
Funding
- Academy of Finland
- EU
- European Research Council
- Sigrid Juselius Foundation
- European Molecular Biology Organization (EMBO)
- Finnish Cancer Organizations
- Turku Graduate School of Biomedical Sciences
- Alexander von Humbold foundation
- EMBO
- National Institutes of Health [T32 DK07449-28, AR49288]
Ask authors/readers for more resources
Regulated activation of integrins is critical for cell adhesion, motility and tissue homeostasis. Talin and kindlins activate beta 1-integrins, but the counteracting inhibiting mechanisms are poorly defined. We identified SHARPIN as an important inactivator of beta 1-integrins in an RNAi screen. SHARPIN inhibited beta 1-integrin functions in human cancer cells and primary leukocytes. Fibroblasts, leukocytes and keratinocytes from SHARPIN-deficient mice exhibited increased beta 1-integrin activity, which was fully rescued by re-expression of SHARPIN. We found that SHARPIN directly binds to a conserved cytoplasmic region of integrin alpha-subunits and inhibits recruitment of talin and kindlin to the integrin. Therefore, SHARPIN inhibits the critical switching of beta 1-integrins from inactive to active conformations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available