Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving transferase
Reexamination Certificate
2001-02-28
2004-05-04
Monshipouri, Maryam (Department: 1652)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving transferase
C435S194000, C435S006120, C435S320100, C435S325000, C435S252300
Reexamination Certificate
active
06730491
ABSTRACT:
BACKGROUND OF THE INVENTION
Phosphate tightly associated with protein has been known since the late nineteenth century. Since then, a variety of covalent linkages of phosphate to proteins have been found. The most common involve esterification of phosphate to serine, threonine, and tyrosine with smaller amounts being linked to lysine, arginine, histidine, aspartic acid, glutamic acid, and cysteine. The occurrence of phosphorylated proteins implies the existence of one or more protein kinases capable of phosphorylating amino acid residues on proteins, and also of protein phosphatases capable of hydrolyzing phosphorylated amino acid residues on proteins.
Protein kinases play critical roles in the regulation of biochemical and morphological changes associated with cellular growth and division (D'Urso, G. et al. (1990)
Science
250: 786-791; Birchmeier. C. et al. (1993)
Bioessays
15: 185-189). They serve as growth factor receptors and signal transducers and have been implicated in cellular transformation and malignancy (Hunter, T. et al. (1992)
Cell
70: 375-387; Posada, J. et al. (1992)
Mol. Biol. Cell
3: 583-592; Hunter, T. et al. (1994)
Cell
79: 573-582). For example, protein kinases have been shown to participate in the transmission of signals from growth-factor receptors (Sturgill, T. W. et al. (1988)
Nature
344: 715-718; Gomez, N. et al. (1991)
Nature
353: 170-173), control of entry of cells into mitosis (Nurse, P. (1990)
Nature
344: 503-508; Maller, J. L. (1991)
Curr. Opin. Cell Biol
. 3: 269-275) and regulation of actin bundling (Husain-Chishti, A. et al. (1988)
Nature
334: 718-721). Protein kinases can be divided into two main groups based on either amino acid sequence similarity or specificity for either serine/threonine or tyrosine residues. A small number of dual-specificity kinases are structurally like the serine/threonine-specific group. Within the broad classification, kinases can be further sub-divided into families whose members share a higher degree of catalytic domain amino acid sequence identity and also have similar biochemical properties. Most protein kinase family members also share structural features outside the kinase domain that reflect their particular cellular roles. These include regulatory domains that control kinase activity or interaction with other proteins (Hanks, S. K. et al. (1988)
Science
241: 42-52).
SUMMARY OF THE INVENTION
The present invention is based, in part, on the discovery of novel protein kinase family members, referred to herein as “2504, 15977, and 14760”. The nucleotide sequence of a cDNA encoding 2504 is shown in SEQ ID NO:1, and the amino acid sequence of a 2504 polypeptide is shown in SEQ ID NO:2. In addition, the nucleotide sequences of the coding region are depicted in SEQ ID NO:3. The nucleotide sequence of a cDNA encoding 15977 is shown in SEQ ID NO:4, and the amino acid sequence of a 15977 polypeptide is shown in SEQ ID NO:5. In addition, the nucleotide sequences of the coding region are depicted in SEQ ID NO:6. The nucleotide sequence of a cDNA encoding 14760 is shown in SEQ ID NO:7, and the amino acid sequence of a 14760 polypeptide is shown in SEQ ID NO:8. In addition, the nucleotide sequences of the coding region are depicted in SEQ ID NO:9.
Accordingly, in one aspect, the invention features a nucleic acid molecule which encodes a 2504, 15977, or 14760 protein or polypeptide, e.g., a biologically active portion of the 2504, 15977, or 14760 protein. In a preferred embodiment the isolated nucleic acid molecule encodes a polypeptide having the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:8. In other embodiments, the invention provides isolated 2504, 15977, or 14760 nucleic acid molecules having the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number 1843. In still other embodiments, the invention provides nucleic acid molecules that are substantially identical (e.g., naturally occurring allelic variants) to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number 1843. In other embodiments, the invention provides a nucleic acid molecule which hybridizes under a stringent hybridization condition described herein to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number 1843. wherein the nucleic acid encodes a full length 2504, 15977, or 14760 protein or an active fragment thereof.
In a related aspect, the invention further provides nucleic acid constructs which include a 2504, 15977, or 14760 nucleic acid molecule described herein. In certain embodiments, the nucleic acid molecules of the invention are operatively linked to native or heterologous regulatory sequences. Also included, are vectors and host cells containing the 2504, 15977, or 14760 nucleic acid molecules of the invention e.g., vectors and host cells suitable for producing 2504, 15977, or 14760 nucleic acid molecules and polypeptides.
In another related aspect, the invention provides nucleic acid fragments suitable as primers or hybridization probes for the detection of 2504, 15977, or 14760-encoding nucleic acids.
In still another related aspect, isolated nucleic acid molecules that are antisense to a 2504, 15977, or 14760 encoding nucleic acid molecule are provided.
In another aspect, the invention features, 2504, 15977, or 14760 polypeptides, and biologically active or antigenic fragments thereof that are useful, e.g., as reagents or targets in assays applicable to treatment and diagnosis of 2504, 15977, or 14760 mediated or related disorders. In another embodiment, the invention provides 2504, 15977, or 14760 polypeptides having a 2504, 15977, or 14760 activity. Preferred polypeptides are 2504, 15977, or 14760 proteins including at least one protein kinase domain, e.g. a serine/threonine kinase domain, and, preferably, having a 2504, 15977, or 14760 activity, e.g., a 2504, 15977, or 14760 activity as described herein.
In other embodiments, the invention provides 2504, 15977, or 14760 polypeptides, e.g., a 2504, 15977, or 14760 polypeptide having the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:8; the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number 1843; an amino acid sequence that is substantially identical to the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:8; or an amino acid sequence encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under a stringent hybridization condition described herein to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number 1843, wherein the nucleic acid encodes a full length 2504, 15977, or 14760 protein or an active fragment thereof.
In a related aspect, the invention further provides nucleic acid constructs which include a 2504, 15977, or 14760 nucleic acid molecule described herein.
In a related aspect, the invention provides 2504, 15977, or 14760 polypeptides or fragments operatively linked to non-2504, 15977, or 14760 polypeptides to form fusion proteins.
In another aspect, the invention features antibodies and antigen-binding fragments thereof, that react with, or more preferably specifically bind 2504, 15977, or 14760 polypeptides.
In another aspect, the invention provides methods of screening for compounds that modulate the expression or activity of the 2504, 15977, or 14760 polypeptides or nucleic acids.
In still another aspect, the invention features a method of modulating (e.g., enhancing or inhibiting) the proliferation, survival, and/or
Curtis Rory A. J.
Kapeller-Libermann Rosana
Meyers Rachel A.
Millennium Pharmaceuticals Inc.
Millennium Pharmaceuticals Inc.
Monshipouri Maryam
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