Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion

  title={Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion},
  author={Camilla Englund and Christina E. Lor{\'e}n and Caroline Grabbe and Gaurav K. Varshney and Fabienne Deleuil and Bengt Hallberg and Ruth H. Palmer},
The Drosophila melanogaster gene Anaplastic lymphoma kinase (Alk) is homologous to mammalian Alk, a member of the Alk/Ltk family of receptor tyrosine kinases (RTKs). We have previously shown that the Drosophila Alk RTK is crucial for visceral mesoderm development during early embryogenesis. Notably, observed Alk visceral mesoderm defects are highly reminiscent of the phenotype reported for the secreted molecule Jelly belly (Jeb). Here we show that Drosophila Alk is the receptor for Jeb in the… 
Jeb/Alk signalling regulates the Lame duck GLI family transcription factor in the Drosophila visceral mesoderm
The results suggest that Lmd is a target of Jeb/Alk signalling in the VM of Drosophila embryos, and the ability of Alk signalling to downregulate Lmd protein requires the N-terminal 140 amino acids.
The ligand Jelly Belly (Jeb) activates the Drosophila Alk RTK to drive PC12 cell differentiation, but is unable to activate the mouse ALK RTK.
The results suggest that either mouse ALK and "mouse Jeb" have co-evolved to the extent that mALK can no longer recognise the Drosophila Jeb ligand or that the mALK RTK has evolved such that it is no longer activated by a Jeb-like molecule in vertebrates.
The bHLH transcription factor Hand is regulated by Alk in the Drosophila embryonic gut.
The scaffolding protein Cnk Interacts with Alk to Promote Visceral Founder Cell Specification in Drosophila
It is reported that the scaffolding protein Cnk interacts directly with Alk via a novel c-terminal binding motif and represents the first molecules downstream of Alk whose loss genocopies the lack of visceral FC-specification of AlK and jeb mutants indicating an essential role in Alk-signalling.
The Zic family homologue Odd-paired regulates Alk expression in Drosophila
Modulation of Alk expression by Opa in the embryonic AS, epidermis and VM is shown and enhancer elements that integrate input from additional TFs, such as Binou (Bin) and Bagpipe (Bap), to regulate VM expression of AlK in a combinatorial manner are identified.
The scaffolding protein Cnk binds to the receptor tyrosine kinase Alk to promote visceral founder cell specification in Drosophila
A critical role is identified for the scaffolding protein Cnk (connector enhancer of kinase suppressor of Ras) in this signaling pathway, which facilitates activation of the receptor tyrosine kinase ALK pathway in the visceral mesoderm of Drosophila larvae.
The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in Drosophila Growth and Learning
dAlk is identified as an upstream activator of dNf1-regulated Ras signaling responsible for several dNF1 defects, and human Alk is implicate as a potential therapeutic target in NF1.
Drosophila Anaplastic Lymphoma Kinase regulates Dpp signalling in the developing embryonic gut.
It is proposed that not only does Alk signalling regulate founder cell specification and thus fusion in the developing visceral muscle, but that Alk also regulates Dpp signalling between the visceral muscle and the endoderm, which provides an elegant mechanism with which to temporally coordinate visceral muscle fusion and later events in midgut development.
DamID transcriptional profiling identifies the Snail/Scratch transcription factor Kahuli as Alk target in the Drosophila visceral mesoderm
A rich dataset of Alk responsive loci in the embryonic VM is reported, the first functional characterization of the Kah transcription factor is provided, and a model in which Kah and Pnt cooperate in embryonic midgut morphogenesis is suggested.
Identification of the Wallenda JNKKK as an Alk suppressor reveals increased competitiveness of Alk-expressing cells
It is shown that Alk expression leads to a growth advantage and induces cell death in surrounding cells, which can be reversed by over-expression of the JNK kinase kinase Wnd.


A crucial role for the Anaplastic lymphoma kinase receptor tyrosine kinase in gut development in Drosophila melanogaster
It is proposed that the main function of Drosophila Alk during early embryogenesis is in visceral mesoderm development, which is the causative agent in non‐Hodgkin's lymphoma.
Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system
Molecular cloning of cDNAs for both the human and mouse ALK proteins reveal that ALK is a novel receptor protein-tyrosine kinase having a putative transmembrane domain and an extracellular domain and shows the greatest sequence similarity to LTK (leukocyte tyrosine Kinase) whose biological function is presently unknown.
DFak56 Is a Novel Drosophila melanogaster Focal Adhesion Kinase*
Drosophila melanogaster FAK homologue DFak56 is described, which maps to band 56D on the right arm of the second chromosome and encodes a phosphoprotein of 140 kDa, which shares strong sequence similarity not only with mammalian p125FAK but also with the more recently described mammalian Pyk2.
ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)
Anaplastic Lymphoma Kinase (ALK) was originally identified as a member of the insulin receptor subfamily of receptor tyrosine kinases that acquires transforming capability when truncated and fused to
rst and its paralogue kirre act redundantly during embryonic muscle development in Drosophila.
Evidence is presented that this is due to functional redundancy between Rst and its paralogue Kirre, which are highly related single-pass transmembrane proteins with five extracellular immunoglobulin domains and three conserved motifs in the intracellular domain.
Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
The 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes to fuse the NPM nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene, ALK, on chromosome 2p23.
MAP kinase in situ activation atlas during Drosophila embryogenesis.
The capacity to follow the active state of these signaling pathways in situ is described by monitoring, with a specific monoclonal antibody, the distribution of the active, dual phosphorylated form of MAP kinase (ERK).
Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo
While the mechanism of ALK activation in non‐Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described.
Myoblast fusion in Drosophila.
  • H. Dworak, H. Sink
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2002
The cellular studies, and the recent genetic and biochemical analyses that uncovered interacting extracellular molecules present on fusing myoblasts and the intracellular effectors that facilitate fusion in Drosophila are reviewed.