Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors

@article{Foehr2000DiscoidinDR,
  title={Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors},
  author={Erik D. Foehr and A Tatavos and Eriko Tanabe and Simona Raffioni and Sara E. Goetz and E Dimarco and Maria De Luca and Ralph A Bradshaw},
  journal={The FASEB Journal},
  year={2000},
  volume={14},
  pages={973 - 981}
}
The discoidin domain receptor (DDR1) is characterized by a discoidin I motif in the extracellular domain, an unusually long cytoplasmic juxtamembrane (JM) region, and a kinase domain that is 45% identical to that of the NGF receptor, TrkA. DDR1 also has a major splice form, which has a 37 amino acid insert in the JM region with a consensus Shc PTB site that is lacking in the shorter receptor. One class of ligands for the DDR receptors has recently been identified as being derived from the… 
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44 Citations

Interaction of discoidin domain receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen‐activated protein kinase and promotes differentiation of macrophages
TLDR
Discoidin domain receptor 1 in response to collagen transduces signals that promote maturation/differentiation of HLA‐DR‐positive antigen‐presenting cells and contributes to the development of adaptive immunity in a tissue microenvironment.
Normal Activation of Discoidin Domain Receptor 1 Mutants with Disulfide Cross-links, Insertions, or Deletions in the Extracellular Juxtamembrane Region
TLDR
The findings indicate that the extracellular juxtamembrane region of DDR1 is exceptionally flexible and does not constrain the basal or ligand-activated state of the receptor, and a plausible mechanism to explain these findings is signaling by DDR1 clusters.
Mapping of Epitopes in Discoidin Domain Receptor 1 Critical for Collagen Binding*
TLDR
It was shown that the discoidin domain was necessary and sufficient for collagen binding, and the entire extracellular domain was essential for transmembrane signaling, and predicted key sites in the collagen-binding epitope of DDR1 and to suggest a potential mechanism of signaling.
Functional analysis of discoidin domain receptor 1: effect of adhesion on DDR1 phosphorylation
TLDR
It is confirmed that endogenous DDR1 is phosphorylated slowly by collagen in adherent T47D and HCT116 cells, the first RTK whose kinetics of phosphorylation is dependent on cellular context and the interaction of the cells with the matrix, rather than cell‐cell contact, is probably responsible for the inhibition of phosphORYlation.
Sensing extracellular matrix: an update on discoidin domain receptor function.
Discoidin domain receptor 1 isoform‐a (DDRla) promotes migration of leukocytes in three‐dimensional collagen lattices
TLDR
It is proposed that the interaction of DDR1a with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense.
Discoidin Domain Receptor 1 Tyrosine Kinase Has an Essential Role in Mammary Gland Development
TLDR
Results suggest that DDR1 is a key mediator of the stromal-epithelial interaction during ductal morphogenesis in the mammary gland.
Discovery of a Potent and Selective DDR1 Receptor Tyrosine Kinase Inhibitor
TLDR
DDR1-IN-1 binds to DDR1 in the ‘DFG-out’ conformation and inhibits DDR1 autophosphorylation in cells at submicromolar concentrations with good selectivity as assessed against a panel of 451 kinases measured using the KinomeScan technology.
Discovery of a Potent and Selective DDR 1 Receptor Tyrosine Kinase Inhibitor
TLDR
A potent and selective DDR1 inhibitor, DDR1IN-1, is found and a mutation in the hinge region of DDR1, G707A, is identified that confers >20-fold resistance to the ability of DDR 1-IN-2 to inhibit DDR1 autophosphorylation and can be used to establish what pharmacology is DDR1-dependent.
Discoidin domain receptors: Micro insights into macro assemblies.
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