Grb14 inhibits FGF receptor signaling through the regulation of PLCγ recruitment and activation

Browaeys-Poly, Edith; Blanquart, Christophe; Perdereau, Dominique; Antoine, Anne-Frédérique; Goenaga, Diana; Luzy, Jean-Philippe; Chen, Huixiong; Garbay, Christiane; Issad, Tarik; Cailliau, Kátia; Burnol, Anne-Françoise

doi:10.1016/j.febslet.2010.09.048

Cited by 19 publications

(18 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CBL also interacts with PI3K, leading to its ubiquitination and degradation (Dufour et al 2008). The adaptor protein Grb14 binds to FGFR phospho-Tyr766 and interferes with phosphorylation and activation of PLCγ (Browaeys-Poly et al 2010).…”

Section: Fgf Signalingmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

View full text Add to dashboard Cite

Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.

show abstract

Section: Fgf Signalingmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

View full text Add to dashboard Cite

show abstract

“…Overexpression of Grb14 inhibited FGF2-mediated proliferation, suggesting that Grb14 functions as a negative regulator of Fgfr signaling (Reilly et al 2000). It has been proposed that Grb14 inhibits Fgfr signaling by preventing recruitment and activation of Plcγ to phosphotyrosine 766 (Browaeys-Poly et al 2010). Grb14 −/− mice are viable and fertile with metabolic phenotypes that are generally attributed to alterations in signaling through the insulin receptor (Cooney et al 2004).…”

Section: Adaptor Protein Grb14mentioning

confidence: 99%

Genetic insights into the mechanisms of Fgf signaling

2016

View full text Add to dashboard Cite

The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo.

show abstract

“…Fgfr1-Plcγ signaling has been implicated in endocytosis of the receptor in vitro (Sorokin et al 1994) and negative regulation of signaling in vivo (Partanen et al 1998). Grb14 is an adaptor protein that binds Tyr766 and Tyr776 (Reilly et al 2000) in order to inhibit Fgfr1-mediated activation of Plcγ (Browaeys-Poly et al 2010).…”

mentioning

confidence: 99%

Fgfr1 regulates development through the combinatorial use of signaling proteins

et al. 2015

View full text Add to dashboard Cite

Fibroblast growth factor (Fgf) signaling governs multiple processes important in development and disease. Many lines of evidence have implicated Erk1/2 signaling induced through Frs2 as the predominant effector pathway downstream from Fgf receptors (Fgfrs), but these receptors can also signal through other mechanisms. To explore the functional significance of the full range of signaling downstream from Fgfrs in mice, we engineered an allelic series of knock-in point mutations designed to disrupt Fgfr1 signaling functions individually and in combination. Analysis of each mutant indicates that Frs2 binding to Fgfr1 has the most pleiotropic functions in development but also that the receptor uses multiple proteins additively in vivo. In addition to Frs2, Crk proteins and Plcγ also contribute to Erk1/2 activation, affecting axis elongation and craniofacial and limb development and providing a biochemical mechanism for additive signaling requirements. Disruption of all known signaling functions diminished Erk1/2 and Plcγ activation but did not recapitulate the peri-implantation Fgfr1-null phenotype. This suggests that Erk1/2-independent signaling pathways are functionally important for Fgf signaling in vivo.

show abstract

Grb14 inhibits FGF receptor signaling through the regulation of PLCγ recruitment and activation

Cited by 19 publications

References 29 publications

Fibroblast growth factor signaling in skeletal development and disease

Fibroblast growth factor signaling in skeletal development and disease

Genetic insights into the mechanisms of Fgf signaling

Fgfr1 regulates development through the combinatorial use of signaling proteins

Contact Info

Product

Resources

About