Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
1998-08-26
2003-09-30
Eyler, Yvonne (Department: 1646)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C435S069100, C435S194000, C436S501000, C514S002600, C536S023500
Reexamination Certificate
active
06627733
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to receptor tyrosine kinases with discoidin-type or like binding domains and nucleic acids encoding such receptor tyrosine kinases. It is noted that the “type” or “like” term that is associated with the names discoidin, discoidin I, and equivalent molecules in this disclosure implies that structural and functional similarities exist between the subject molecule's binding domain and the binding domain found in discoidin, discoidin I, and equivalent molecules.
2. Description of the Background Art
Certain extracellular molecules influence cellular growth, differentiation or development via activation of receptor tyrosine kinases (Bishop, J. M. (1991)
Cell
64, 235-248 and Hunter, T. (1991)
Meth. Enz
. 200, 3-37, which are incorporated herein by reference). Receptor tyrosine kinases are composed of an extracellular ligand binding domain and a cytoplasmic catalytic domain that allow for specific decoding of extracellular signals and initiation of intracellular biochemical effects. A large number of cDNAs for putative receptor tyrosine kinases have been cloned and sequenced (Hanks, S. K. & Quinn, A. M. (1991)
Meth. Enz
. 200, 38-62, which is incorporated herein by reference). With rare exception (Shier, P. & Watt, V. M. (1989)
J. Biol. Chem
. 264, 14605-14608, which is incorporated herein by reference), sequence similarities in extracellular domains have not suggested the type of ligand that might activate a given receptor. Nevertheless, the diversity of receptor tyrosine kinase extracellular domains implies that there are a large number of as yet unidentified extracellular molecules that can regulate receptor tyrosine kinase activity and, by extension, growth, differentiation or development. Identification of these ligands is crucial for a comprehensive understanding of these fundamental biological processes. It is clear that researchers are only beginning to understand the complexity of the extracellular signals that can activate receptor tyrosine kinases. Also, little is known about the fundamental process of information exchange across the membrane to initiate the intracellular cascade of biochemical effectors. Disclosed here is the cDNA cloning and characterization of a novel breast carcinoma cell protein with a primary structure which suggests that this protein is a receptor tyrosine kinase with an unusual mechanism of transmembrane signaling. An extracellular domain of this protein is similar to the lectin-like or type protein or specifically the carbohydrate-binding protein discoidin I.
SUMMARY OF THE INVENTION
An object of the present invention is to present a polypeptide having both a first domain with carbohydrate or discoidin I-type binding activity and a second domain with tyrosine kinase activity.
Another object of the present invention is to disclose a nucleic acid sequence that encodes for a polypeptide having a first domain with carbohydrate or discoidin I-type binding activity and a second domain with tyrosine kinase activity.
A further object of the present invention is to make known a marker that may be utilized to predict and diagnose tumors of the breast and lung.
Still another object of the present invention is to describe a nucleic acid sequence that encodes a polypeptide having both discoidin I-type ligand binding characteristics and tyrosine kinase activity that can be utilized in immunological and inhibitory regulation of associated tumors.
Yet a further object of the present invention is to disclose a polypeptide having both discoidin I-type ligand binding characteristics and tyrosine kinase activity that can be utilized in immunological and inhibitory regulation of associated tumors.
Disclosed is a novel breast carcinoma tyrosine phosphoprotein, DDR (Discoidin Domain Receptor), that defines a novel class of receptor tyrosine kinases. The DDR cDNA predicts a C-terminal tyrosine kinase domain and an N-terminal domain similar to the
Dictyostelium discoideum
lectin named discoidin or more specifically discoidin I. These domains are connected by an extraordinary hydrophilic proline/glycine-rich domain, which is interrupted by a predicted transmembrane sequence. This extended proline/glycine-rich region suggests an unusual geometry of interaction with ligand or substrates. Discoidin I-type domains are also found in other proteins, including coagulation factors V and VIII. Discoidin I-type domains may interact with specific cell surface molecules. SEQ ID NO: 1 designates the nucleotide sequence of the present invention, SEQ ID NO: 2 designates the polypepteide or protein sequence of the present invention, and SEQ ID NO: 3 designates the probe utilized in the subject invention.
REFERENCES:
patent: 5677144 (1997-10-01), Ullrich
patent: 6051397 (2000-04-01), Ullrich et al.
Edman Jeffrey C.
Johnson Jeffrey D.
Rutter William J.
Brannock Michael
Eyler Yvonne
Townsend and Townsend / and Crew LLP
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