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Receptor Tyrosine Kinases in Development: Insights from Drosophila - PubMed

  • ️Tue Jan 01 2019

Review

Receptor Tyrosine Kinases in Development: Insights from Drosophila

Sarah Mele et al. Int J Mol Sci. 2019.

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.

Keywords: Drosophila melanogaster; cell fate; cell signaling; cytokine; growth factor; receptor tyrosine kinase (RTK).

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Conflict of interest statement

Authors declare no conflicts of interest.

Figures

Figure 1
Figure 1

General overview of receptor tyrosine kinase activation, signaling, and the cell-fate decisions they influence. The binding of growth factors (inputs) in the extracellular milieu induces conformation changes in the receptor monomer that enables dimerization. Enzymatic autophosphorylation (circled p) by intracellular tyrosine kinase domains in trans results in recruitment of one or more signal transduction cascades. These relay the signal to effectors that determine cell fates (outputs). Mitogen-activated protein kinase, MAPK; phosphatidylinositol 3-kinase–protein kinase B, PI3K–Akt; phospholipase C gamma–protein kinase C, PLCgamma–PKC; Janus kinase and signal transducer and activator of transcription, JAK–STAT.

Figure 2
Figure 2

Pvr-Pvf1 mediated collective migration of border cells in the Drosophila ovary. Pvf1 emanating from the posteriorly located oocyte stimulates the collective migration of the border cell cluster toward its anterior boundary during oogenesis. Activation of Pvr by Pvf1 (black dots) at the leading-edge drives actin polymerization within invasive foci (inset). This is maintained by local receptor recycling (solid arrows) following endocytosis, complex disassembly (dotted arrow), then trafficking back to the cell surface.

Figure 3
Figure 3

Torso signaling in embryonic patterning and the timing of developmental transitions. (A) Activation of Torso by its ligand Trunk at the termini of the early embryo triggers the de-repression of zygotic target genes and the specification of terminal cell fate. Torso signaling location is determined by Torso-like (Tsl), which is present only at the termini and is thought to permit the release of Trunk into the perivitelline space. (B) During larval development, Torso is activated by a second ligand, called PTTH, to trigger development transitions, including the initiation of metamorphosis. Torso is expressed in the major endocrine organ, the prothoracic gland (PG), which is directly innervated by two pairs of PTTH producing neurons from the larval brain. PTTH production and/or release is gated by clock neurons. Mitogen-activated protein kinase, MAPK; extracellular signal regulated kinase, ERK; corpus allatum, CA; prothoracic gland, PG; corpora cardiaca, CC; prothoracicotropic hormone, PTTH; short neuropeptide F, sNPF; pigment dispersing factor, PDF.

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