Receptor Tyrosine Kinases in Development: Insights from Drosophila

Abstract

Cell-to-cell communication mediates a plethora of cellular decisions and behaviors that are crucial for the correct and robust development of multicellular organisms. Many of these signals are encoded in secreted hormones or growth factors that bind to and activate cell surface receptors, to transmit the cue intracellularly. One of the major superfamilies of cell surface receptors are the receptor tyrosine kinases (RTKs). For nearly half a century RTKs have been the focus of intensive study due to their ability to alter fundamental aspects of cell biology, such as cell proliferation, growth, and shape, and because of their central importance in diseases such as cancer. Studies in model organisms such a Drosophila melanogaster have proved invaluable for identifying new conserved RTK pathway components, delineating their contributions, and for the discovery of conserved mechanisms that control RTK-signaling events. Here we provide a brief overview of the RTK superfamily and the general mechanisms used in their regulation. We further highlight the functions of several RTKs that govern distinct cell-fate decisions in Drosophila and explore how their activities are developmentally controlled.

Signaling Pathways That Regulate the Crustacean Molting Gland

“…The LAF pro signaling pathway has not been fully characterized, but parallels with the action of Dilp8 on the insect PG suggest a common mechanism. Dilp8 is one of eight insulin-like peptides (ILPs) in D. melanogaster (74)(75)(76)(77)(78). The ILP superfamily consists of insulin, insulin-like growth factors (IGFs), and relaxin-like peptides (38,71).…”

“…Growth factor signaling is mediated by the Ras/Raf/MAPK and PI3K/PDK1/Akt pathways (Figure 4) (132). In insects, growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor, (PDGF) and vascular endothelial growth factor (VEGF), serve many functions critical for embryogenesis, molting, and metamorphosis (76). Activation of the Ras/Raf/MAPK pathway stimulates ecdysteroidogenesis in the insect PG (97,106).…”

“…There are about 58 RTKs in 20 subfamilies in mammals, with fewer in arthropods. D. melanogaster , for example, has 20 RTKs distributed among 14 subfamilies ( 76 ). RTKs have an extracellular ligand-binding domain, a single-pass transmembrane domain, and an intracellular tyrosine kinase domain (TKD).…”

Coordination Among Multiple Receptor Tyrosine Kinase Signals ControlsDrosophilaDevelopmental Timing and Body Size

“…This result is consistent with at least partial overlap between Alk, Pvr and Torso signaling through Ras/ERK activation. In addition to Ras/Erk, Pi3K/Akt is another signaling pathway activated by RTKs (Mele and Johnson, 2019). A well-studied RTK that activates Pi3K/Akt signaling in the PG is InR, which conveys nutritional signal to the PG and promotes PG growth (Colombani et al, 2005;Mirth et al, 2005).…”

Spatiotemporal sensitivity of embryonic heart specification to FGFR signaling inDrosophila

“…Ligand-binding leads to FGFR homo-dimerisation, initiating trans-phosphorylation events which ultimately activates transcription of several target genes (Fantl et al .,1993). This transcriptional response regulates different cellular responses, such as changes in cell morphology, proliferation, adhesion, migration and differentiation (Spivak-Kroizman et al ., 1994; Mohammadi et al ., 1996; Thisse & Thisse, 2005; Teven et al ., 2014; Mele & Johnson, 2020). Due to their involvement in key cellular processes, FGFRs when mutated can promote cancer development and progression (Turner & Grose, 2010; Wesche et al ., 2011; Presta et al ., 2017).…”