期刊
JOURNAL OF CELL BIOLOGY
卷 151, 期 6, 页码 1269-1279出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.151.6.1269
关键词
chemotaxis; signal transduction; phosphatidylinositol 3-kinase; receptor protein-tyrosine kinases; platelet-derived growth factor
类别
资金
- NIGMS NIH HHS [GM R01-51457, F32 GM020488-01, F32 GM020488] Funding Source: Medline
The directed movement of fibroblasts towards locally released platelet-derived growth factor (PDGF) is a critical event in wound healing. Although recent studies have implicated polarized activation of phosphoinositide (PI) 3-kinase in G protein-mediated chemotaxis, the role of 3' PI lipids in tyrosine kinase-triggered chemotaxis is not well understood. Using evanescent wave microscopy and green fluorescent protein-tagged Akt pleckstrin homology domain (GFP-AktPH) as a molecular sensor, we show that application of a shallow PDGF gradient triggers a markedly steeper gradient in 3' PI lipids in the adhesion zone of fibroblasts, Polar GFP-AktPH gradients, as well as a new type of radial gradient, were measured from front to rear and from the periphery to the center of the adhesion zone, respectively. A strong spatial correlation between polarized 3' PI production and rapid membrane spreading implicates 3' PI lipids as a direct mediator of polarized migration. Analysis of the temporal changes of 3' PI gradients in the adhesion zone revealed a fast diffusion coefficient (0.5 mum(2)/s) and short lifetime of 3' Pls of <1 min. Together, this study suggests that the tyrosine kinase-coupled directional movement of fibroblasts and their radial membrane activity are controlled by local generation and rapid degradation of 3' PI second messengers.
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