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Dev Biol. 2019 Mar 1;447(1):71-89. doi: 10.1016/j.ydbio.2017.10.017. Epub 2017 Oct 26.

Feedback regulation of RTK signaling in development.

Author information

1
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco 94143, USA.
2
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
3
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: natalia.jura@ucsf.edu.
4
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco 94143, USA; Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco 94143, USA. Electronic address: ophir.klein@ucsf.edu.

Abstract

Precise regulation of the amplitude and duration of receptor tyrosine kinase (RTK) signaling is critical for the execution of cellular programs and behaviors. Understanding these control mechanisms has important implications for the field of developmental biology, and in recent years, the question of how augmentation or attenuation of RTK signaling via feedback loops modulates development has become of increasing interest. RTK feedback regulation is also important for human disease research; for example, germline mutations in genes that encode RTK signaling pathway components cause numerous human congenital syndromes, and somatic alterations contribute to the pathogenesis of diseases such as cancers. In this review, we survey regulators of RTK signaling that tune receptor activity and intracellular transduction cascades, with a focus on the roles of these genes in the developing embryo. We detail the diverse inhibitory mechanisms utilized by negative feedback regulators that, when lost or perturbed, lead to aberrant increases in RTK signaling. We also discuss recent biochemical and genetic insights into positive regulators of RTK signaling and how these proteins function in tandem with negative regulators to guide embryonic development.

KEYWORDS:

Developmental control; Feedback regulation; RASopathies; Receptor tyrosine kinases; Signaling pathways; Sprouty

PMID:
29079424
PMCID:
PMC5920792
[Available on 2020-03-01]
DOI:
10.1016/j.ydbio.2017.10.017
[Indexed for MEDLINE]

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