DLC1 interacts with 14-3-3 proteins to inhibit RhoGAP activity and block nucleocytoplasmic shuttling
| Autor: | Angelika Hausser, Patrik Erlmann, Gerlinde Holeiter, Simone Schmid, Anke Theil, Rolf-Peter Scholz, Monilola A. Olayioye, Jennifer Regner, Ruth Jähne |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
RHOA
Recombinant Fusion Proteins RHOB Molecular Sequence Data Active Transport Cell Nucleus RhoC GTPase Cell Line chemistry.chemical_compound Phorbol Esters Serine Animals Humans Protein Isoforms Amino Acid Sequence Protein Kinase C Protein kinase C Cell Nucleus biology Tumor Suppressor Proteins GTPase-Activating Proteins Signal transducing adaptor protein Cell Biology Cell biology Enzyme Activation 14-3-3 Proteins chemistry Biochemistry Phosphoserine biology.protein DLC1 Protein Binding |
| Zdroj: | Journal of Cell Science. 122:92-102 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.036251 |
| Popis: | Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|