| First Author | Komander D | Year | 2008 |
| Journal | EMBO J | Volume | 27 |
| Issue | 23 | Pages | 3175-85 |
| PubMed ID | 18946488 | Mgi Jnum | J:200394 |
| Mgi Id | MGI:5508588 | Doi | 10.1038/emboj.2008.226 |
| Citation | Komander D, et al. (2008) Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure. EMBO J 27(23):3175-85 |
| abstractText | The ROCK-I serine/threonine protein kinase mediates the effects of RhoA to promote the formation of actin stress fibres and integrin-based focal adhesions. ROCK-I phosphorylates the unconventional G-protein RhoE on multiple N- and C-terminal sites. These phosphorylation events stabilise RhoE, which functions to antagonise RhoA-induced stress fibre assembly. Here, we provide a molecular explanation for multi-site phosphorylation of RhoE from the crystal structure of RhoE in complex with the ROCK-I kinase domain. RhoE interacts with the C-lobe alphaG helix of ROCK-I by means of a novel binding site remote from its effector region, positioning its N and C termini proximal to the ROCK-I catalytic site. Disruption of the ROCK-I:RhoE interface abolishes RhoE phosphorylation, but has no effect on the ability of RhoE to disassemble stress fibres. In contrast, mutation of the RhoE effector region attenuates RhoE-mediated disruption of the actin cytoskeleton, indicating that RhoE exerts its inhibitory effects on ROCK-I through protein(s) binding to its effector region. We propose that ROCK-I phosphorylation of RhoE forms part of a feedback loop to regulate RhoA signalling. |
