Disease relevance of Ptp61F

• Mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP-2, causes Noonan syndrome (NS), an autosomal dominant disorder with pleomorphic developmental abnormalities [1].
• Using Drosophila to decipher how mutations associated with human branchio-oto-renal syndrome and optical defects compromise the protein tyrosine phosphatase and transcriptional functions of eyes absent [2].

High impact information on Ptp61F

• DLAR is a receptor-like, transmembrane protein-tyrosine phosphatase in Drosophila that is expressed almost exclusively by developing neurons [3].
• The csw gene encodes a putative nonreceptor protein tyrosine phosphatase covalently linked to two N-terminal SH2 domains, which is similar to the mammalian PTP1C protein [4].
• corkscrew encodes a putative protein tyrosine phosphatase that functions to transduce the terminal signal from the receptor tyrosine kinase torso [4].
• We describe the isolation of seven different protein-tyrosine phosphatase (PTPase) cDNAs from Drosophila embryos, three of which are primarily expressed in the central nervous system (CNS) [5].
• We find that the cdc25 sequence shows weak but significant homology to a phylogenetically diverse group of protein tyrosine phosphatases. cdc25 itself is a very specific protein tyrosine phosphatase [6].

Biological context of Ptp61F

• Alternative splicing gives rise to a nuclear protein tyrosine phosphatase in Drosophila [7].
• This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock [8].
• DPTP61F transcription is detected only after stage 6 of oogenesis [9].
• After stage 10B these transcripts are transported to the oocyte; thus ovarian transcription of DPTP61F may reflect a maternal contribution of the mRNA for later use during embryogenesis [9].
• MetaBlasts: tracing protein tyrosine phosphatase gene family roots from Man to Drosophila melanogaster and Caenorhabditis elegans genomes [10].

Anatomical context of Ptp61F

• Moreover, in vivo analysis demonstrates that disrupted dBRWD3 and overexpressed Ptp61F function as suppressors of leukaemia-like blood cell tumours [11].
• These carboxyl-terminal sequences govern the targeting of each protein tyrosine phosphatase either to a cytoplasmic membrane or to the nucleus [7].
• A recent series of genetic studies in the Drosophila visual system has demonstrated roles for several cell adhesion molecules, including N-cadherin and the receptor protein tyrosine phosphatase LAR in proper synaptic targeting of photoreceptor axons [12].
• The leech receptor protein tyrosine phosphatase HmLAR2 is concentrated in growth cones and is involved in process outgrowth [13].
• The neural receptor protein tyrosine phosphatase DPTP69D is required during periods of axon outgrowth in Drosophila [14].

Associations of Ptp61F with chemical compounds

• In addition to multiple human disease gene homologues, we have found the tyrosine phosphatase Ptp61F and the Drosophila homologue of BRWD3, a bromo-domain-containing protein disrupted in leukaemia [11].
• This signaling pathway is mediated by the serine/threonine kinase D-raf and a protein tyrosine phosphatase corkscrew (csw) [15].

Other interactions of Ptp61F

• A novel Drosophila receptor-like protein tyrosine phosphatase gene, DPTP4E, was isolated and characterized [16].
• We have cloned and characterized a novel cytoplasmic protein tyrosine phosphatase, PTP-ER, which is related to mammalian PCPTP1, LC-PTP/HePTP, and STEP tyrosine phosphatases [17].
• Like mutations in the protein tyrosine phosphatase gene Dlar, strong Ptp69D alleles cause the ISNb nerve to bypass its muscle targets [14].
• Signaling by ectopically expressed Drosophila Src64 requires the protein-tyrosine phosphatase corkscrew and the adapter downstream of receptor kinases [18].
• In addition to these molecules we have characterized the putative protein tyrosine phosphatase Corkscrew as a positive transducer downstream of Torso [19].

Analytical, diagnostic and therapeutic context of Ptp61F

• The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments [8].
• The spatial and temporal expression of seven Drosophila protein tyrosine phosphatase genes during oogenesis was examined by whole mount in-situ hybridization of antisense RNA probes to ovaries [9].
• Over the past several years an impressive number of receptor-like protein tyrosine phosphatase (RPTPase) family members have been identified by molecular cloning, and undoubtedly many more will follow [20].

References