Abstract
Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein-protein and protein-lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving She and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β- overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.
| Original language | English |
|---|---|
| Pages (from-to) | 3729-3744 |
| Number of pages | 16 |
| Journal | Molecular Biology of the Cell |
| Volume | 17 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2006 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
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Phosphoinositide 3-kinase C2β regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms. / Katso, Roy M.; Pardo, Olivier E.; Palamidessi, Andrea; Franz, Clemens M.; Marinov, Marin; De Laurentiis, Angela; Downward, Julian; Scita, Giorgio; Ridley, Anne J.; Waterfield, Michael D.; Arcaro, Alexandre.
In: Molecular Biology of the Cell, Vol. 17, No. 9, 09.2006, p. 3729-3744.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phosphoinositide 3-kinase C2β regulates cytoskeletal organization and cell migration via Rac-dependent mechanisms
AU - Katso, Roy M.
AU - Pardo, Olivier E.
AU - Palamidessi, Andrea
AU - Franz, Clemens M.
AU - Marinov, Marin
AU - De Laurentiis, Angela
AU - Downward, Julian
AU - Scita, Giorgio
AU - Ridley, Anne J.
AU - Waterfield, Michael D.
AU - Arcaro, Alexandre
PY - 2006/9
Y1 - 2006/9
N2 - Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein-protein and protein-lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving She and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β- overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.
AB - Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein-protein and protein-lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving She and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β- overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.
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UR - http://www.scopus.com/inward/citedby.url?scp=33748329395&partnerID=8YFLogxK
U2 - 10.1091/mbc.E05-11-1083
DO - 10.1091/mbc.E05-11-1083
M3 - Article
C2 - 16775008
AN - SCOPUS:33748329395
VL - 17
SP - 3729
EP - 3744
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 9
ER -