TY - JOUR
T1 - SWAP-70 is a guanine-nucleotide-exchange factor that mediates signalling of membrane ruffling
AU - Shinohara, Masahiro
AU - Terada, Yoh
AU - Iwamatsu, Akihiro
AU - Shinohara, Azusa
AU - Mochizuki, Naoki
AU - Higuchi, Maiko
AU - Gotoh, Yukiko
AU - Ihara, Sayoko
AU - Nagata, Satoshi
AU - Itoh, Hiroshi
AU - Fukui, Yasuhlsa
AU - Jessberger, Rolf
N1 - Funding Information:
We thank T. Adachi-Yamada, G. Campbell, M. Calleja, A. Cantarero, S. González-Crespo, M. Gonzalez-Gaitan, E. Hafen, A. Jazwinska, E. Martin-Blanco, B. Müller, E. Sánchez-Herrero, M. Suzanne and P. ten Dijke for fly stocks and antibodies; R. González for technical assistance; S. Campuzano for help with the TUNEL technique; C. Sánchez for help with confocal microscopy; and M. Calleja, O. Gerlitz, E. Hafen, G. Hausmann, P. Lawrence, F. Martin, B. Müller, D. Nellen, E. Sánchez-Herrero, H. Stocker and members of our laboratories for discussions. E.M. was supported by a postdoctoral fellowship from the Comunidad Autónoma de Madrid and the Swiss National Science Foundation.
Funding Information:
We thank B. Mayer and M. Matsuda for useful suggestions and critical reading of the manuscript, and T. Nagase (Kazusa DNA Research Institute) for supplying the KIAA0640 clone. This work was supported by grants-in-aid for scientific research to Y.F. from the Ministry of Education, Science, Sports, and Culture of Japan, and by an NIH grant to R.J.
PY - 2002
Y1 - 2002
N2 - Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor stimulation, generates a lipid second messenger, phosphatidylinositol-3, 4, 5-trisphosphate (PtdIns(3, 4, 5)P3). PtdIns(3, 4, 5)P3 is instrumental in signalling pathways that trigger cell activation, cytoskeletal rearrangement, survival and other reactions. However, some targets of PtdIns(3, 4, 5)P3 are yet to be discovered. We demonstrate that SWAP-70, a unique signalling protein, specifically binds PtdIns(3, 4, 5)P. On stimulation by growth factors, cytoplasmic SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the ability to bind PtdIns(3, 4, 5)P3 blocked membrane ruffling induced by epidermal growth factor or platelet-derived growth factor. SWAP-70 shows low homology with Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3, 4, 5)P3-dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts showed impaired membrane ruffling after stimulation with epidermal growth factor, and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac.
AB - Phosphoinositide-3-OH kinase (PI(3)K), activated through growth factor stimulation, generates a lipid second messenger, phosphatidylinositol-3, 4, 5-trisphosphate (PtdIns(3, 4, 5)P3). PtdIns(3, 4, 5)P3 is instrumental in signalling pathways that trigger cell activation, cytoskeletal rearrangement, survival and other reactions. However, some targets of PtdIns(3, 4, 5)P3 are yet to be discovered. We demonstrate that SWAP-70, a unique signalling protein, specifically binds PtdIns(3, 4, 5)P. On stimulation by growth factors, cytoplasmic SWAP-70, which is dependent on PI(3)K but independent of Ras, moved to cell membrane rearrangements known as ruffles. However, mutant SWAP-70 lacking the ability to bind PtdIns(3, 4, 5)P3 blocked membrane ruffling induced by epidermal growth factor or platelet-derived growth factor. SWAP-70 shows low homology with Rac-guanine nucleotide exchange factors (GEFs), and catalyses PtdIns(3, 4, 5)P3-dependent guanine nucleotide exchange to Rac. SWAP-70-deficient fibroblasts showed impaired membrane ruffling after stimulation with epidermal growth factor, and failed to activate Rac fully. We conclude that SWAP-70 is a new type of Rac-GEF which, independently of Ras, transduces signals from tyrosine kinase receptors to Rac.
UR - https://www.scopus.com/pages/publications/0037129193
U2 - 10.1038/416759a
DO - 10.1038/416759a
M3 - Article
C2 - 11961559
AN - SCOPUS:0037129193
SN - 0028-0836
VL - 416
SP - 759
EP - 763
JO - Nature
JF - Nature
IS - 6882
ER -