| First Author | Ge L | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 36 | Pages | 34418-26 |
| PubMed ID | 12821670 | Mgi Jnum | J:85273 |
| Mgi Id | MGI:2673740 | Doi | 10.1074/jbc.M300573200 |
| Citation | Ge L, et al. (2003) A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem 278(36):34418-26 |
| abstractText | Cell motility during wound healing and inflammation is often dependent on the ability of the cell to sense a gradient of agonist. The first step in this process is the extension of a pseudopod in the direction of the agonist, and a diverse set of signals mediate pseudopod extension by different receptors. We have reported previously that protease-activated receptor-2 (PAR-2), a proinflammatory receptor that is highly expressed in motile cells such as neutrophils, macrophages, and tumor cells, is one of a growing family of receptors that utilizes a beta-arrestin-dependent mechanism for activation of the 42-44-kDa members of the MAPK family (extracellular signal-regulated kinases 1 and 2; ERK1/2). beta-Arrestin-bound PAR-2 serves as a scaffold to sequester a pool of activated ERK1/2 in the cytosol; however, a specific role for the sequestered kinase activity has not been established. We now show that PAR-2 activation promotes ERK1/2- and beta-arrestin-dependent reorganization of the actin cytoskeleton, polarized pseudopodia extension, and chemotaxis. Using subcellular fractionation, confocal microscopy, and physical isolation of pseudopodial proteins, we demonstrate that the previously identified PAR-2/beta-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia, where it appears to prolong ERK1/2 activation. These studies suggest that the formation of a beta-arrestin/ERK1/2 signaling complex at the leading edge may be involved in localized actin assembly and chemotaxis and provide the first example of a distinct cellular consequence of beta-arrestin-sequestered ERK1/2 activity. |
