Premium
EDG‐1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration
Author(s) -
Rosenfeldt Hans M.,
Hobson John P.,
Maceyka Michael,
Olivera Ana,
Nava Victor E.,
Milstien Sheldon,
Spiegel Sarah
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0523com
Subject(s) - lamellipodium , microbiology and biotechnology , platelet derived growth factor receptor , focal adhesion , proto oncogene tyrosine protein kinase src , sphingosine kinase 1 , cell migration , receptor tyrosine kinase , biology , sphingosine , tyrosine kinase , signal transduction , growth factor , sphingosine 1 phosphate , cell , receptor , biochemistry
Sphingosine‐1‐phosphate (SPP), formed by sphingosine kinase, is the ligand for EDG‐1, a GPCR important for cell migration and vascular maturation. Here we show that cytoskeletal rearrangements, lamel‐lipodia extensions, and cell motility induced by platelet‐derived growth factor (PDGF) are abrogated in EDG‐1 null fibroblasts. However, EDG‐1 appears to be dis‐pensable for mitogenicity and survival effects, even those induced by its ligand SPP and by PDGF. Furthermore, PDGF induced focal adhesion formation and activation of FAK, Src, and stress‐activated protein kinase 2, p38, were dysregulated in the absence of EDG‐1. In contrast, tyrosine phosphorylation of the PDGFR and activation of extracellular signal regulated kinase (ERK1/2), important for growth and survival, were unaltered. Our results suggest that EDG‐1 functions as an integrator linking the PDGFR to lamellipo‐dia extension and cell migration. PDGF, which stimulates sphingosine kinase, leading to increased SPP levels in many cell types, also induces translocation of sphingosine kinase to membrane ruffles. Hence, recruitment of sphingosine kinase to the cell's leading edge and localized formation of SPP may spatially and temporally stimulate EDG‐1, resulting in activation and integration of downstream signals important for directional movement toward chemoattractants, such as PDGF. These results may also shed light on the vital role of EDG‐1 in vascular maturation.—Rosenfeldt, H. M., Hobson, J. P., Maceyka, M., Olivera, A., Nava, V. E., Milstien, S., Spiegel, S. EDG‐1 links the PDGF receptor to SRC and focal adhesion kinase activation leading to lamellipodia formation and cell migration. FASEB J. 15, 2649–2659 (2001)