title: Functions of the ectodomain and cytoplasmic tyrosine phosphatase domains of receptor protein tyrosine phosphatase Dlar in vivo.
abstract: The receptor protein tyrosine phosphatase (PTPase) Dlar has an ectodomain consisting of three immunoglobulin (Ig)-like domains and nine fibronectin type III (FnIII) repeats and a cytoplasmic domain consisting of two PTPase domains, membrane-proximal PTP-D1 and C-terminal PTP-D2. A series of mutant Dlar transgenes were introduced into the Drosophila genome via P-element transformation and were then assayed for their capacity to rescue phenotypes caused by homozygous loss-of-function genotypes. The Ig-like domains, but not the FnIII domains, are essential for survival. Conversely, the FnIII domains, but not the Ig-like domains, are required during oogenesis, suggesting that different domains of the Dlar ectodomain are involved in distinct functions during Drosophila development. All detectable PTPase activity maps to PTP-D1 in vitro. The catalytically inactive mutants of Dlar were able to rescue Dlar(-/-) lethality nearly as efficiently as wild-type Dlar transgenes, while this ability was impaired in the PTP-D2 deletion mutants DlarDeltaPTP-D2 and Dlar(bypass). Dlar-C1929S, in which PTP-D2 has been inactivated, increases the frequency of bypass phenotype observed in Dlar(-/-) genotypes, but only if PTP-D1 is catalytically active in the transgene. These results indicate multiple roles for PTP-D2, perhaps by acting as a docking domain for downstream elements and as a regulator of PTP-D1.
authors.affiliation: Dana-Farber Cancer Institute/Harvard Cancer Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Neil X
authors.initials: NX
authors.lastname: Krueger
authors.forename: R Sreekantha
authors.initials: RS
authors.lastname: Reddy
authors.forename: Karl
authors.initials: K
authors.lastname: Johnson
authors.forename: Jack
authors.initials: J
authors.lastname: Bateman
authors.forename: Nancy
authors.initials: N
authors.lastname: Kaufmann
authors.forename: Daniella
authors.initials: D
authors.lastname: Scalice
authors.forename: David
authors.initials: D
authors.lastname: Van Vactor
authors.forename: Haruo
authors.initials: H
authors.lastname: Saito
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009866:Oogenesis; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054557:Receptor-Like Protein Tyrosine Phosphatases; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D005982:Glutathione Transferase; C117978:Lar protein, Drosophila; D017027:Protein Tyrosine Phosphatases; D054557:Receptor-Like Protein Tyrosine Phosphatases