Growth factor homolog ZVEGF4
AssigneeZymoGenetics, Inc.
InventorsTeresa Gilbert, Charles E. Hart, Paul O. Sheppard, Debra G. Gilbertson
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Abstract
Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 70% identical to residues 52-179 of SEQ ID NO:2 or residues 258-370 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.
Claims54
An isolated polypeptide of at least 15 amino acid residues comprising an epitope-bearing portion of a protein of SEQ ID NO:2.
An isolated polypeptide comprising a sequence of amino acids of the formula R1x—R2y—R3z, wherein:
- R1 is a polypeptide of from 100 to 130 residues in length, is at least 70% identical to residues 52-179 of SEQ ID NO:2, and comprises a sequence motif C[KR]Y[DNE][WYF]X{11,15}G[KR][WYF]C (SEQ ID NO:4) corresponding to residues 109-131 of SEQ ID NO:2;
- R2 is a polypeptide at least 90% identical to residues 180-257 of SEQ ID NO:2;
- R3 is a polypeptide at least 70% identical in amino acid sequence to residues 258-370 of SEQ ID NO:2 and comprises cysteine residues at positions corresponding to residues 272, 302, 306, 318, 360, and 362 of SEQ ID NO:2;
- a glycine residue at a position corresponding to residue 304 of SEQ ID NO:2;
- and a sequence motif CX{18,33}CXGXCX{6,33}CX{20,50}CXC (SEQ ID NO:3) corresponding to residues 272-362 of SEQ ID NO:2;
- and
- each of x, y, and z is individually 0 or 1, subject to the limitations that:
- at least one of x and z is 1;
- and
- if x and z are each 1, then y is 1.
An isolated protein comprising a first polypeptide operably linked to a second polypeptide, wherein said first polypeptide comprises a sequence of amino acids of the formula R1x—R2y—R3z, wherein:
- R1 is a polypeptide of from 100 to 130 residues in length, is at least 70% identical to residues 52-179 of SEQ ID NO:2, and comprises a sequence motif C[KR]Y[DNE][WYF]X{11,15}G[KR][WYF]C (SEQ ID NO:4) corresponding to residues 109-131 of SEQ ID NO:2;
- R2 is a polypeptide at least 90% identical to residues 180-257 of SEQ ID NO:2;
- R3 is a polypeptide at least 70% identical in amino acid sequence to residues 258-370 of SEQ ID NO:2 and comprises cysteine residues at positions corresponding to residues 272, 302, 306, 318, 360, and 362 of SEQ ID NO:2;
- a glycine residue at a position corresponding to residue 304 of SEQ ID NO:2;
- and a sequence motif CX{25,33}CXGXCX{10,33}CX{20,50}CXC (SEQ ID NO:3) corresponding to residues 272-362 of SEQ ID NO:2;
- and
- each of x, y, and z is individually 0 or 1, subject to the limitations that:
- at least one of x and z is 1;
- and
- if x and z are each 1, then y is 1,
- and wherein said protein modulates cell proliferation, apoptosis, differentiation, metabolism, or migration.
An isolated protein produced by a method comprising:
- (a) culturing a host cell containing an expression vector comprising the following operably linked elements:
- a transcription promoter;
- a DNA segment encoding a polypeptide comprising a sequence of amino acid residues selected from the group consisting of:
- i) residues 52-370 of SEQ ID NO:2;
- ii) residues 52-253 of SEQ ID NO:2;
- iii) residues 180-370 of SEQ ID NO:2;
- and
- iii) residues 258-370 of SEQ ID NO:2;
- and
- a transcription terminator,
- under conditions whereby the DNA segment is expressed;
- and
- (b) recovering from the cell the protein product of expression of the DNA construct.
An isolated polynucleotide of up to approximately 4.4 kb in length, wherein said polynucleotide encodes a polypeptide comprising a sequence of amino acids of the formula R1x—R2y—R3z, wherein:
- R1 is a polypeptide of from 100 to 130 residues in length, is at least 70% identical to residues 52-179 of SEQ ID NO:2, and comprises a sequence motif C[KR]Y[DNE][WYF]X{11,15}G[KR][WYF]C (SEQ ID NO:4) corresponding to residues 109-131 of SEQ ID NO:2;
- R2 is a polypeptide at least 90% identical to residues 180-257 of SEQ ID NO:2;
- R3 is a polypeptide at least 70% identical in amino acid sequence to residues 258-370 of SEQ ID NO:2 and comprises cysteine residues at positions corresponding to residues 272, 302, 306, 318, 360, and 362 of SEQ ID NO:2;
- a glycine residue at a position corresponding to residue 304 of SEQ ID NO:2;
- and a sequence motif CX{25,33}CXGXCX{10,33}CX{20,50}CXC (SEQ ID NO:3) corresponding to residues 272-362 of SEQ ID NO:2;
- and
- each of x, y, and z is individually 0 or 1, subject to the limitations that:
- at least one of x and z is 1;
- and
- if x and z are each 1, then y is 1.
A method for detecting a genetic abnormality in a patient, comprising:
- obtaining a genetic sample from a patient;
- incubating the genetic sample with a polynucleotide comprising at least 14 contiguous nucleotides of SEQ ID NO:
- 1 or the complement of SEQ ID NO:
- 1, under conditions wherein said polynucleotide will hybridize to a complementary polynucleotide sequence, to produce a first reaction product;
- and
- comparing said first reaction product to a control reaction product, wherein a difference between said first reaction product and said control reaction product is indicative of a genetic abnormality in the patient.
A polypeptide comprising a sequence selected from the group consisting of:
- residues 46-234 of SEQ ID NO:33 operably linked to residues 258-370 of SEQ ID NO:2;
- residues 46-170 of SEQ ID NO:33 operably linked to residues 180-370 of SEQ ID NO:2;
- residues 52-257 of SEQ ID NO:2 operably linked to residues 235-345 of SEQ ID NO:33;
- and
- residues 52-179 of SEQ ID NO:2 operably linked to residues 171-345 of SEQ ID NO:33.
Dependencies are inferred from the claim text.