Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving hydrolase
Patent
1996-08-09
1998-10-13
Teng, Sally
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving hydrolase
435196, 435 721, 435 691, 4353201, 435 18, 536 235, 530350, C12Q 142, C12N 1555, C07K 14435
Patent
active
058210750
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to the isolation and cloning of nucleic acids encoding two novel protein tyrosine phosphatases (PTPs). Specifically, the present invention relates to the isolation and cloning of two PTPs from human glioblastoma cDNA which have been designated PTPL1 and GLM-2. The present invention provides isolated PTP nucleic acid sequences; isolated PTP anti-sense sequences; vectors containing such nucleic acid sequences; cells, cell lines and animal hosts transformed by a recombinant vector so as to exhibit increased, decreased, or differently regulated expression of the PTPs; isolated probes for identifying sequences substantially similar or homologous to such sequences; substantially pure PTP proteins and variants or fragments thereof; antibodies or other agents which bind to these PTPs and variants or fragments thereof; methods of assaying for activity of these PTPs; methods of assessing the regulation of PTPL1 or GLM-2; and methods of identifying and/or testing drugs which may affect the expression or activity of these PTPs.
BRIEF DESCRIPTION OF THE BACKGROUND ART
Protein tyrosine phosphorylation plays an essential role in the regulation of cell growth, proliferation and differentiation (reviewed in Hunter, T. (1987) Cell 50:823-8291). This dynamic process is modulated by the counterbalancing activities of protein tyrosine kinases (PTKS) and protein tyrosine phophatases (PTPs). The recent elucidation of intracellular signaling pathways has revealed important roles for PTKS. Conserved domains like the Src homology 2 (SH2) (Suh, P.-G., et al., (1988) Proc. Natl. Acad Sci. (USA) 85,5419-5423) and the Src homology 3 (SH3) (Mayer, B. J., et al., (1988) Nature 352:272-275) domains have been found to determine the interaction between activated PTKS and signal transducing molecules (reviewed in Pawson, T., and Schiessinger, J. (1993) Current Biol. 3:434-442; Koch, C. A., et al., (1991) Science 252:668-674). The overall effect of such protein interactions is the formation of signaling cascades in which phosphorylation and dephosphorylation of proteins on tyrosine residues are major events. The involvement of PTPs in such signaling cascades is beginning to emerge from studies on the regulation and mechanisms of action of several representatives of this broad family of proteins.
Similarly to PTKS, PTPs can be classified according to their secondary structure into two broad groups, i.e. cytoplasmic and transmembrane molecules (reviewed in Charbonneau, H., and Tonks, N. K. (1992) Annu. Rev. Cell Biol. 8:463-493; Pot, D. A., and Dixon, J. E. (1992) Biochim. Biophys. Acta 1136:35-43). Transmembrane PTPs have the structural organization of receptors and thus the potential to initiate cellular signaling in response to external stimuli. These molecules are characterized by the presence of a single transmembrane segment and two tandem PTP domains; only two examples of transmembrane PTPs that have single PTP domains are known, HPTP-P (Krueger, N. X., et al., (1990) EMBO J. 9:3241-3252) and DPTP10D (Tian, S. -S., et al., (1991) Cell 67:675-685).
Nonreceptor PTPs display a single catalytic domain and contain, in addition, non-catalytic amino acid sequences which appear to control intracellular localization of the molecules and which may be involved in the determination of substrate specificity (Mauro, L. J., and Dixon, J. E. (1994) TIBS 19:151-155) and have also been suggested to be regulators of PTP activity (Charbonneau, H., and Tonks, N. K. (1992) Annu. Rev. Cell Biol. 8:463-493). PTP1B (Tonks, N. K., et al., (1988) J. Biol. Chem. 263:6731-6737) is localized to the cytosolic face of the endoplasmic reticulum via its C-terminal 35 amino acids (Frangioni, J. V., et al., (1992) Cell 68:545-560). The proteolytic cleavage of PTP1B by the calcium dependent neutral protease calpain occurs upstream from this targeting sequence, and results in the relocation of the enzyme from the endoplasmic reticulum to the cytosol; such relocation is concomitant with a two-fold stimulation of PTP1B enzymati
REFERENCES:
Lewin, Science, 237, 1570, Sep. 1987.
Reeck et al., Cell, 50, 667, Aug. 1987.
Saras et al., "Cloning and characterization of PTPL1, a protein tyrosine phosphatase with similarities to cytoskeletal-associated proteins", Sep. 30, 1994, pp. 24082-24089, J.Biol.Chem., vol. 269, No. 39.
Maekawa et al., "Molecular cloning of a novel protein-tyrosine phosphatase containing a membrane-binding domain and GLGF repeats", Jan. 10, 1994, pp. 200-206, Febs Letters, vol. 337.
Yung et al., "Differential expression of protein tyrosine phosphatases in primary human brain tumors", Mar. 1993, p. 527, Proc. Am. Assoc. Cancer Research, vol. 34.
Lombroso et al., "Characterization of a protein-tyrosine phosphatase enriched in striatum",Aug. 1991, pp. 7242-7246, Proc. Natl. Acad. Sciences, vol. 88.
Toews et al., "Evidence for involvement of tyrosine phosphorylation in serum-induced sensitization of cyclic AMP accumulation in C62B rat glioma cells", 1992, p. A1075, Faseb J., vol. 6, No. 4.
Yang et al., "Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin and talin", 1991, pp. 5949-5953, Proc. Natl. Acad. Sciences, vol. 88.
Gu et al., "Identification cloning, and expression of cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1", 1991, pp. 5867-5871, Proc. Natl. Acad Sciences, vol. 88.
Adachi et al., "Molecular cloning and chromosomal mapping of a human protein-tyrosine phosphatase LC-PTP", Aug. 14, 1992, pp. 1607-1615, Biochem. Biophys. Res. Commun., vol. 186, No. 3.
Claesson-Welsh Lana
Gonez Leonel Jorge
Heldin Carl-Henrik
Saras Jan
Teng Sally
The Ludwig Institute for Cancer Research
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