Dtrk, a Drosophila gene related to the trk family of neurotrophin receptors, encodes a novel class of neural cell adhesion molecule.

Pulido, Daniel; Campuzano, Sonsoles; Koda, Toshiaki; Modolell, Juan; Barbacid, Mariano

doi:10.1002/j.1460-2075.1992.tb05067.x

Cited by 150 publications

(101 citation statements)

References 70 publications

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“…S2 insect cells overexpressing Ark formed multicellular aggregates that could be blocked by excess recombinant Ark ECD (6). Similar results could be achieved upon overexpression of D-Trk or protein phosphatase-and -in the same S2 cells (7)(8)(9). These data raise the possibility that receptor tyrosine kinases and transmembrane phosphatases may function both as adhesion molecules and as elements of the signaling cascade.…”

supporting

confidence: 62%

GAS6 Mediates Adhesion of Cells Expressing the Receptor Tyrosine Kinase Axl

McCloskey

Fridell²,

Attar³

et al. 1997

Journal of Biological Chemistry

126

103

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Axl is a receptor tyrosine kinase that contains both immunoglobulin and fibronectin III repeats in its extracellular domain reminiscent of cell adhesion molecules. Expression of the receptor tyrosine kinase Axl in the 32D myeloid cell line permits aggregation of cells in response to treatment with the native ligand GAS6; this aggregation was not observed in untreated 32D-Axl cells nor in treated parental cells. This aggregation can be blocked by the addition of excess Axl extracellular domain peptide and does not require intracellular Axl kinase activity. Cell surface binding activity of GAS6 was mapped to distinct plasma membrane interacting domains that are separate from the GAS6 motifs that engage the Axl receptor. This suggests that aggregation is mediated by a heterotypic intercellular mechanism whereby cell-bound GAS6 interacts with Axl receptor on an adjacent cell. This mechanism is supported by our observation that GAS6 binds to 32D parental cells which then permits their aggregation with untreated 32D-Axl cells. We have recently demonstrated that the GAS6-Axl interaction does not initiate mitogenesis in 32D cells. When considered with the adhesion results, these data suggest that an important biological function of the Axl-GAS6 interaction is to mediate cell-cell binding.

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supporting

confidence: 62%

GAS6 Mediates Adhesion of Cells Expressing the Receptor Tyrosine Kinase Axl

McCloskey

Fridell²,

Attar³

et al. 1997

Journal of Biological Chemistry

126

103

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“…MT1-MMP directly cleaves the PKP 621 2LI sequence in an exposed region of PTK7, generating the N-terminal, soluble PTK7 ectodomain. Because PTK7 readily oligomerizes through its ectodomain (10,52), membrane PTK7 forms a complex either with itself or with the solubilized ectodomain or with some yet to be identified adaptor protein(s) (2, 13, 39 -41, 43, 48). It is likely that these different complex types elicit the dissimilar downstream signaling events and that these signaling events differentially regulate multiple cell functions, including PCP and directional motility, in processes as diverse as cancer cell invasion and embryonic cell migration during gastrulation in eukaryotes (13,18,28,30).…”

Section: Discussionmentioning

confidence: 99%

Potential Relation of Aberrant Proteolysis of Human Protein Tyrosine Kinase 7 (PTK7) chuzhoi by Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) to Congenital Defects

Golubkov

Aleshin

Strongin

2011

Journal of Biological Chemistry

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Membrane PTK7 pseudo-kinase plays an essential role in planar cell polarity and the non-canonical Wnt pathway in vertebrates. Recently, a new N-ethyl-N-nitrosourea-induced mutant named chuzhoi (chz) was isolated in mice. chz embryos have severe birth defects, including a defective neural tube, defective heart and lung development, and a shortened anterior-posterior body axis. The chz mutation was mapped to the Ala-Asn-Pro tripeptide insertion into the junction region between the fifth and the sixth Ig-like domains of PTK7. Unexpectedly, chz reduced membrane localization of the PTK7 protein. We hypothesized and then proved that the chz mutation caused an insertion of an additional membrane type 1 matrix metalloproteinase cleavage site in PTK7 and that the resulting aberrant proteolysis of chz affected the migratory parameters of the cells. It is likely that aberrations in the membrane type 1 matrix metalloproteinase/PTK7 axis are detrimental to cell movements that shape the body plan and that chz represents a novel model system for increasing our understanding of the role of proteolysis in developmental pathologies, including congenital defects.About three of every 100 babies born in the United States have congenital abnormalities. Congenital abnormalities are ranked 34th of the top 50 causes of total death in the United States. Debilitating cardiovascular and nervous system defects jointly represent 40% of birth defects. The death toll of congenital abnormalities (0.58%) roughly equals that of stomach, skin, or oral cancers. Mechanistic research into birth defects is required to more efficiently contribute to prevention and correction of these disorders.The canonical, ␤-catenin-dependent and non-canonical, ␤-catenin-independent Wnt signaling pathways are conserved in eukaryotes and are critical for the diverse events in embryonic development and disease. The non-canonical Wnt/planar cell polarity (PCP) 2 signaling controls cell organization within the tissue plane (1, 2). The Wnt/PCP signaling affects the actin cytoskeleton via RhoA GTPase activation through dishevelled associated activator of morphogenesis 1 (DAAM1) and dishevelled activator of morphogenesis 2 (DAAM2). The first PCP signaling events occur at a gastrulation stage of embryogenesis. These events regulate the polarized directed cell movement to accomplish convergent extension for the anterior-posterior body axis elongation, neural tube closure, and craniofacial morphogenesis (3-6). Convergent extension failure results in a shortened anterior-posterior body axis and widened lateral axis (convergent extension phenotype), a defective neural system, and craniofacial abnormalities.Ubiquitously expressed PTK7 (also called colon carcinoma kinase-4 (CCK-4)) is a Wnt coreceptor and a regulator of PCP in vertebrates (7-13). Membrane PTK7 includes seven extracellular Ig domains, a transmembrane region, and a catalytically inert cytoplasmic tyrosine kinase (PTK) domain (8,9,11,14). PTK7 is evolutionary conserved in humans and mice and also chicken klingon (KLG...

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“…Drosophila trk homologue promotes cell adhesion by homophilic interaction of the extracellular domains (Pulido et al, 1992). Tannahill et al (1995) have demonstrated that coating of cell culture dishes with trkA ectodomain inhibits neurite outgrowth, indicating that this domain in¯uences neuronal adhesion.…”

Section: Discussionmentioning

confidence: 99%

Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells

et al. 1999

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We have investigated the eects of the truncated trkB receptor isoform T1 (trkB.T1) by transient transfection into mouse N2a neuroblastoma cells. We observed that expression of trkB.T1 leads to a striking change in cell morphology characterized by outgrowth of ®lopodia and processes. A similar morphological response was also observed in SH-SY5Y human neuroblastoma cells and NIH3T3 ®broblasts transfected with trkB.T1. N2a cells lack endogenous expression of trkB isoforms, but express barely detectable amounts of its ligands, brainderived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). The morphological change was ligand-independent, since addition of exogenous BDNF or NT-4 or blockade of endogenous trkB ligands did not in¯uence this response. Filopodia and process outgrowth was signi®cantly suppressed when full-length trkB.TK+ was cotransfected together with trkB.T1 and this inhibitory eect was blocked by tyrosine kinase inhibitor K252a. Transfection of trkB.T1 deletion mutants showed that the morphological response is dependent on the extracellular, but not the intracellular domain of the receptor. Our results suggest a novel ligand-independent role for truncated trkB in the regulation of cellular morphology.

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Dtrk, a Drosophila gene related to the trk family of neurotrophin receptors, encodes a novel class of neural cell adhesion molecule.

Cited by 150 publications

References 70 publications

GAS6 Mediates Adhesion of Cells Expressing the Receptor Tyrosine Kinase Axl

GAS6 Mediates Adhesion of Cells Expressing the Receptor Tyrosine Kinase Axl

Potential Relation of Aberrant Proteolysis of Human Protein Tyrosine Kinase 7 (PTK7) chuzhoi by Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) to Congenital Defects

Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells

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