» Articles » PMID: 35606055

Pulling Back the Curtain: The Hidden Functions of Receptor Tyrosine Kinases in Development

Overview
Publisher Elsevier
Date 2022 May 23
PMID 35606055
Authors
Affiliations
Soon will be listed here.
Abstract

Receptor tyrosine kinases (RTKs) are a conserved superfamily of transmembrane growth factor receptors that drive numerous cellular processes during development and in the adult. Upon activation, multiple adaptors and signaling effector proteins are recruited to binding site motifs located within the intracellular domain of the RTK. These RTK-effector interactions drive subsequent intracellular signaling cascades involved in canonical RTK signaling. Genetic dissection has revealed that alleles of Fibroblast Growth Factor receptors (FGFRs) that lack all canonical RTK signaling still retain some kinase-dependent biological activity. Here we examine how genetic analysis can be used to understand the mechanism by which RTKs drive multiple developmental processes via canonical signaling while revealing noncanonical activities. Recent data from both FGFRs and other RTKs highlight potential noncanonical roles in cell adhesion and nuclear signaling. The data supporting such functions are discussed as are recent technologies that have the potential to provide valuable insight into the developmental significance of these noncanonical activities.

Citing Articles

Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial maturity.

OLoughlin E, Zhang Y, Chiasson-MacKenzie C, Dave P, Rheinbay E, Stott S bioRxiv. 2024; .

PMID: 39282270 PMC: 11398422. DOI: 10.1101/2024.08.30.610360.


Diverse signaling pathways and endocytic trafficking regulate mesoderm development.

Clark J, Soriano P Genes Dev. 2024; 38(9-10):393-414.

PMID: 38834239 PMC: 11216173. DOI: 10.1101/gad.351593.124.


Diverse signaling pathways and endocytic trafficking regulate early mesoderm development.

Clark J, Soriano P bioRxiv. 2024; .

PMID: 38405698 PMC: 10888970. DOI: 10.1101/2024.02.16.580629.


Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.

Guo Y, Xiang P, Sun X, Liu W, Zhou J, Yin B Signal Transduct Target Ther. 2024; 9(1):32.

PMID: 38351062 PMC: 10864363. DOI: 10.1038/s41392-024-01742-2.


FRS2-independent GRB2 interaction with FGFR2 is not required for embryonic development.

Clark J, Soriano P bioRxiv. 2023; .

PMID: 36993499 PMC: 10055321. DOI: 10.1101/2023.03.23.534012.


References
1.
Li X, Padhan N, Sjostrom E, Roche F, Testini C, Honkura N . VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread. Nat Commun. 2016; 7:11017. PMC: 4814575. DOI: 10.1038/ncomms11017. View

2.
Tallquist M, French W, Soriano P . Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development. PLoS Biol. 2003; 1(2):E52. PMC: 261889. DOI: 10.1371/journal.pbio.0000052. View

3.
Beauvais D, Burbach B, Rapraeger A . The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells. J Cell Biol. 2004; 167(1):171-81. PMC: 2172512. DOI: 10.1083/jcb.200404171. View

4.
Bruggemann Y, Karajannis L, Stanoev A, Stallaert W, Bastiaens P . Growth factor-dependent ErbB vesicular dynamics couple receptor signaling to spatially and functionally distinct Erk pools. Sci Signal. 2021; 14(683). DOI: 10.1126/scisignal.abd9943. View

5.
Treisman R . Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev. 1994; 4(1):96-101. DOI: 10.1016/0959-437x(94)90097-3. View