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  • Original Paper
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Src is required for cell migration and shape changes induced by fibroblast growth factor 1

Abstract

Fibroblast growth factor 1 (FGF-1) is a potent chemotactic factor and induces tyrosine phosphorylation of a cortical actin-associated protein (cortactin). The tyrosine phosphorylation of cortactin induced by FGF-1 requires the tyrosine residues 421, 482 and 466, which are targeted by the protein tyrosine kinase Src in vitro. Furthermore, FGF-1 is unable to induce tyrosine phosphorylation of cortactin within the cells derived from Src knockout mice (Src−/−), indicating that Src is required for the tyrosine phosphorylation of cortactin induced by FGF-1. Although Src−/− cells are able to undergo rapid proliferation, they are impaired to respond to FGF-1 for the shape change and cell migration. Morphological analysis further reveals that FGF-1 fails to induce the formation of polarized lamellipodia and the translocation of cortactin into the leading edge of Src−/− cells. Consistent with the mitogenic response to FGF-1, the lack of Src does not affect the tyrosine phosphorylation of Snt (or Frs2), a FGF-1 early signaling protein that links to Ras. Therefore, our data support the notion that Src and cortactin participate in a FGF signal pathway for cell migration and shape change rather than mitogenesis.

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Abbreviations

F-actin:

filamentous actin

FGF:

fibroblast growth factor

DMI:

defined serum-free medium supplemented with insulin

PAGE:

polyacrylamide gel electrophoresis

FITC:

fluorescein-isothiocyanate

PLC:

phospholipase C

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Acknowledgements

We thank Dr Soriano Phillipe for providing Src knockout and normal mouse embryonic fibroblasts. We acknowledge the help of Dr Christian Haudenschild in confocal image analysis. We also thank Ms Yamei Gao and Ms Diana Norman for the photography, and Ms Donna Sobieski for the critical reading of the manuscript. This work was supported by National Institutes of Health grant R29 HL52753 and US Army grant DAMD17-98-8278 (X Zhan).

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Liu, J., Huang, C. & Zhan, X. Src is required for cell migration and shape changes induced by fibroblast growth factor 1. Oncogene 18, 6700–6706 (1999). https://doi.org/10.1038/sj.onc.1203050

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