Alternatively spliced FGFR-1 isoforms differentially modulate endothelial cell activation of c-YES
Abstract
Ligand activation of fibroblast growth factor receptor-1 (FGFR-1) induces an angiogenic response following activation of multiple intracellular signaling substrates, including the Src family of nonreceptor tyrosine kinases (SFK). However, the direct association between FGFR-1 and SFK and the involvement of SFK in FGFR-1-dependent cell proliferation have been controversial. Structural variants of FGFR-1 are generated by alternative splicing which results in two major isoforms, containing either three (FGFR-1alpha) or two (FGFR-1beta) immunoglobulin-like domains in the extracellular region. To determine whether alternatively spliced FGFR-1 isoforms differentially activate SFK, we have examined FGF receptor-negative endothelial cells stably transfected with human cDNA encoding either FGFR-1alpha or FGFR-1beta. Transient activation of c-YES, the predominant SFK expressed in these endothelial cells, was restricted to FGFR-1beta transfectants following exposure to acidic fibroblast growth factor (FGF-1). Co-immunoprecipitation studies revealed that c-YES directly associated with FGFR-1beta. The Src homology (SH)2 domain (and not the SH3 domain) of c-YES was able to recognize tyrosine phosphorylated FGFR-1beta. FGFR-1beta-specific act...Continue Reading
References
Citations
Splice Variants of the RTK Family: Their Role in Tumour Progression and Response to Targeted Therapy
Related Concepts
Related Feeds
Alternative splicing
Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.
Cadherins and Catenins
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.