Disease relevance of Ptp69D

• The PTPase-like domains of HPTP alpha, beta and delta expressed in Escherichia coli had tyrosine phosphatase activities [1].

High impact information on Ptp69D

• The receptor tyrosine phosphatases DPTP69D and DPTP99A are expressed on motor axons in Drosophila embryos [2].
• In mutant embryos lacking DPTP69D protein, motor neuron growth cones stop growing before reaching their muscle targets, or follow incorrect pathways that bypass these muscles [2].
• We show a receptor tyrosine phosphatase, PTP69D, is required for lamina target specificity [3].
• Genetic mosaics, transgene rescue, and immunolocalization indicate PTP69D functions in R1-R6 growth cones [3].
• By using consensus sequence probes, two additional receptor-linked PTPase genes, DLAR and DPTP, were isolated from Drosophila melanogaster [4].

Biological context of Ptp69D

• To understand the regulation of cell proliferation by tyrosine phosphorylation, characterization of protein tyrosine phosphatases (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) is essential [4].
• The analysis of double mutant phenotypes shows that DPTP10D and DPTP69D are necessary for repulsion of growth cones from the midline of the embryonic central nervous system [5].
• In a large-scale saturation mutagenesis performed using this system, we recovered new alleles of the gene encoding the receptor tyrosine phosphatase PTP69D [6].
• Published data show that three of these (DLAR, DPTP69D, DPTP99A) regulate motor axon guidance decisions during embryonic development [7].
• Our observations suggest that the export of DPTP69D mRNA from the nucleus is temporally regulated during oogenesis [8].

Anatomical context of Ptp69D

• We propose PTP69D promotes R1-R6 targeting in response to extracellular signals by dephosphorylating substrate(s) in R1-R6 growth cones [3].
• These targeting errors are difficult to reconcile with models in which PTP69D plays an instructive role in photoreceptor axon targeting, as previously proposed [6].
• In the optic lobes, DPTP69D is localized to the neuropils of the lamina and medulla, and to an array of parallel thick bundles that may be the transmedullary fibers of the developing lobula complex [9].

Associations of Ptp69D with chemical compounds

• Site-directed mutagenesis showed that a conserved cysteine residue is essential for PTPase activity [4].

Other interactions of Ptp69D

• DPTP52F, DPTP10D and DPTP69D have partially redundant roles in regulation of guidance decisions made by axons within the ISN and ISNb motor nerves [10].
• Three RPTPs, known as DLAR, DPTP69D, and DPTP99A, have been genetically characterized thus far [5].
• These data define three major HRP proteins as neurotactin, fasciclin I, and an R-PTP, DPTP69D [9].
• In support of this hypothesis, we demonstrate that SHP-2, a vertebrate PTPase similar to Csw and previously implicated in RTK signaling, encodes the functional vertebrate homologue of Csw [11].
• One of these, corkscrew (csw), encodes an SH2 domain-containing PTPase that appears to be a homolog of mammalian PTP1D [12].

References