Fibroblast growth factor signaling in Caenorhabditis elegans

Abstract

Growth factor receptor tyrosine kinases (RTKs), such as the fibroblast growth factor receptor (FGFR), play a major role in how cells communicate with their environment. FGFR signaling is crucial for normal development, and its misregulation in humans has been linked to developmental abnormalities and cancer. The precise molecular mechanisms by which FGFRs transduce extracellular signals to effect specific biologic responses is an area of intense research. Genetic analyses in model organisms have played a central role in our evolving understanding of these signal transduction cascades. Genetic studies in the nematode C. elegans have contributed to our knowledge of FGFR signaling by identifying genes involved in FGFR signal transduction and linking their gene products together into signaling modules. This review will describe FGFR-mediated signal transduction in C. elegans and focus on how these studies have contributed to our understanding of how FGFRs orchestrate the assembly of intracellular signaling pathways.

FGF negatively regulates muscle membrane extension inCaenorhabditis elegans

“…Twenty-four genes required for guidance were targeted in an RNAi pilot screen using RP1 worms (see Materials and methods and Table S1 in the supplementary material). sem-5, which encodes a small adapter protein that is orthologous to Grb2 and functions downstream of receptor tyrosine kinases (Borland et al, 2001;Clark et al, 1992;Moghal and Sternberg, 2003;Stern et al, 1993), was the only RNAi target that resulted in EMEs (Fig. 1).…”

“…Numerous genes function downstream of egl-15, including the adapter proteins sem-5(Grb2), soc-1(Gab1) and soc-2(Shoc-2/Sur-8), the non-receptor tyrosine phosphatase ptp-2(Shp2), the Ras guanine nucleotide exchange factor sos-1 (Son of Sevenless), and the Ras-family GTPase let-60 (Ras) (Borland et al, 2001). We determined that soc-2(RNAi), ptp-2(RNAi) and let-60(RNAi) each induced EMEs (Fig.…”

Signalling by the FGFR-like tyrosine kinase, Kringelchen, is essential for bud detachment inHydra vulgaris

“…Phosphorylation of docking proteins recruits additional signalling proteins and induces, for example, activation of the Ras/MAPK pathway (Kouhara et al, 1997). FGFR exert pleiotropic effects on cultured cells and embryonic tissues of mainly mesodermal origin in vertebrates, C. elegans and Drosophila (Skaer, 1997;Affolter and Shilo, 2000;Borland et al, 2001). Particularly important for FGFR function are three Ig-like loops in the extracellular ligand binding domain, of which loops II and III form the binding sites for FGF ligands and mediate ligand-induced dimerization.…”

Lipoprotein receptors and a Disabled family cytoplasmic adaptor protein regulate EGL-17/FGF export in C. elegans

“…Spitz, a transmembrane epidermal growth factor (EGF), is held within the ER until Star chaperones it to the Golgi apparatus, where it then encounters Rhomboid-1, which triggers proteolytic cleavage and allows Spitz to move to the cell surface (Lee et al 2001). Most fibroblast growth factors (FGFs) act cell nonautonomously to coordinate cell migrations, proliferation, and fate specification during wound healing, angiogenesis, tumor metastasis, and development (Friesel and Maciag 1995;Goldfarb 1996;Sutherland et al 1996;Borland et al 2001). The majority of FGFs contain standard signal sequences for secretion by the ER-Golgi pathway.…”