Human protein tyrosine phosphatase polynucleotides,...

Details Human protein tyrosine phosphatase polynucleotides,... Human protein tyrosine phosphatase polynucleotides,...

2001-07-18

2004-08-03

Saidha, Tekchand (Department: 1652)

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Transferase other than ribonuclease

C435S252300, C435S320100, C536S023200

Reexamination Certificate

active

06770466

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel human protein tyrosine phosphatase (PTPase) proteins. More specifically, isolated nucleic acid molecules are provided encoding novel PTPase polypeptides. Novel PTPase polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human FTPase polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to these novel PTPase polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention.
BACKGROUND OF THE INVENTION
A wide-range of cellular activities are achieved through the opposing actions of phosphorylation and dephosphorylation of target proteins, mediated by kinases and phosphatases, respectively. Such cellular activities include cell adhesion, cellular signaling, cellular proliferation, and cellular differentiation.
Typically, Protein Tyrosine Phosphatases (PTPases) contain at least one conserved catalytic PTPase domain of approximately 240 amino acids, characterized by the following signature: [I/V]HCxAGxxR[S/T]G. During the phosphatase catalytic activity, the phosphate moiety of the substrate undergoes nucleophilic attack from the cysteinyl residue, resulting in the removal of a phosphate group attached to a tyrosine residue (Neel, B. G., and N. K. Tonks,
Curr. Opin. Cell Biol.,
9:193-204 (1997)).
This large and diverse family of proteins can be sub-divided into the intracellular PTPases and the transmembrane PTPases. The intracellular PTPases, such as hematopoietic cell protein (HCP) tyrosine phosphatase (or SHP), contain one PTPase domain flanked by regulatory sequences involved in protein-protein interactions, cellular localization, and/or enzyme activity. The transmembrane PTPases, such as CD45, contain a transmembrane domain followed by one or more intracellular PTPase domains. It is thought that the transmembrane PTPases are involved in transducing signals across the plasma membrane (M. Streuli,
Curr. Opin. Cell Biol.,
8:182-88 (1996)).
Protein Tyrosine Phosphatases have been found to be involved in a wide range of biological activities. Schmidt et al. found a murine PTPase expressed by osteoclasts that, upon inhibition by Alendronate (ALN), inhibited in vitro osteoclast formation and bone resorption (Schmidt, A., et al.,
Proc. Nat. Acad. Sci
USA, 93:3068-73 (1996)). This PTPase could be a valuable target for inhibitors that prevent bone resorption by osteoclasts.
It has further been found that some Receptor Protein Tyrosine Phosphatases (RPTPs) of Drosophila have profound effects on the growth and guidance of developing nervous systems. Disruption of the RPTP DPTP69D in Drosophila results in pupal lethality. In mutant embryos, motor neuron growth cones are defective in their ability to recognize target muscle groups, or to conversly follow pathways that avoid these targets. Likewise, DLAR mutations leading to the loss of function result in nerve development that is unable to migrate to the appropriate muscle target and innervate it (Neel, B. G., and N. K. Tonks,
Curr. Opin. Cell Biol,
9:193-204 (1997)).
Further, it has been found that the transmembrane PTPase CD45 is required for T-cell receptor signaling. B and T-cells deficient for CD45 demonstrate that CD45 is necessary for T and B lymphocyte activation through their antigen receptors. Knock-out mice that do not express the larger CD45 isoforms lack thymocyte maturation, and have functionally impaired T cells, among other disorders (M. Streuli,
Curr. Opin. Cell Biol,
8:182-88 (1996)).
Thus there exists a clear need for identifying and exploiting novel Protein Tyrosine Phosphatase family members. Although structurally related, such proteins may possess diverse and multifaceted functions in a variety of cell and tissue types. The purified Protein Tyrosine Phosphatase polypeptides of the invention are useful as research tools useful for the identification, characterization and purification of additional molecules involved in cell signaling, and regulation thereof. Furthermore, the identification of new Protein Tyrosine Phosphatases permits the development of a range of derivatives, agonists and antagonists at the nucleic acid and protein levels which in turn have applications in the treatment and diagnosis of a wide-range of conditions such as cellular signaling, neurite outgrowth, cell adhesion, and tissue-healing disorders.
SUMMARY OF THE INVENTION
The present invention includes isolated nucleic acid molecules comprising, or alternatively, consisting of a polynucleotide sequence disclosed in the sequence listing and/or contained in a human cDNA plasmid described in Table 1 and deposited with the American Type Culture Collection (ATCC). Fragments, variants, and derivatives of these nucleic acid molecules are also encompassed by the invention. The present invention also includes isolated nucleic acid molecules comprising, or alternatively, consisting of, a polynucleotide encoding PTPase polypeptides. The present invention further includes PTPase polypeptides encoded by these polynucleotides. Further provided for are amino acid sequences comprising, or alternatively, consisting of, PTPase polypeptides as disclosed in the sequence listing and/or encoded by the human cDNA plasmids described in Table 1 and deposited with the ATCC. Antibodies that bind these polypeptides are also encompassed by the invention. Polypeptide fragments, variants, and derivatives of these amino acid sequences are also encompassed by the invention, as are polynucleotides encoding these polypeptides and antibodies that bind these polypeptides.
DETAILED DESCRIPTION
Tables
Table 1 summarizes ATCC Deposits, Deposit dates, and ATCC designation numbers of deposits made with the ATCC in connection with the present application. Table 1 further summarizes the information pertaining to each “Gene No.” described below, including cDNA clone identifier, the type of vector contained in the cDNA clone identifier, the nucleotide sequence identifier number, nucleotides contained in the disclosed sequence, the location of the 5′ nucleotide of the start codon of the disclosed sequence, the amino acid sequence identifier number, and the last amino acid of the ORF encoded by the disclosed sequence.
Table 2 indicates public ESTs, of which at least one, two, three, four, five, ten, or more of any one or more of these public EST sequences are optionally excluded from certain embodiments of the invention.
Table 3 summarizes the expression profile of polynucleotides corresponding to the clones disclosed in Table 1. The first column provides a unique clone identifier, “cDNA Plasmid:V”, for a cDNA clone related to each contig sequence disclosed in Table 1. Column 2, “Library Code” shows the expression profile of tissue and/or cell line libraries which express the polynucleotides of the invention. Each Library Code in column 2 represents a tissue/cell source identifier code corresponding to the Library Code and Library description provided in Table 4. Expression of these polynucleotides was not observed in the other tissues and/or cell libraries tested. One of skill in the art could routinely use this information to identify tissues which show a predominant expression pattern of the corresponding polynucleotide of the invention or to identify polynucleotides which show predominant and/or specific tissue expression.
Table 4, column 1, provides the Library Code disclosed in Table 3, column 2. Column 2 provides a description of the tissue or cell source from which the corresponding library was derived. Library codes corresponding to diseased tissues are indicated in column 3 with the word “disease”. The u

Affiliated with

Also associated with

Rating

Human protein tyrosine phosphatase polynucleotides,... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Human protein tyrosine phosphatase polynucleotides,..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Human protein tyrosine phosphatase polynucleotides,... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3351724