Growth factor with acts through Erb B-4 RTK

Abstract

A novel ErbB-4 ligand, referred to herein as Neuregulin-4 (NRG-4) is disclosed as well as polynucleotide sequences encoding NRG-4, oligonucleotides and oligonucleotide analogs derived from polynucleotide sequences, a display library displaying short peptides derived from NRG-4, antibodies recognizing NRG-4, peptides or peptide analogs derived from NRG-4, and pharmaceutical compositions and methods of employing peptides or peptide analogs, oligonucleotides and oligonucleotide analogs, and/or polynucleotide sequences to up-regulate or down-regulate ErbB-4 receptor activity (signaling).

1 - 69 . (canceled)  
     
     
         70 . A method of diagnosing a disease, condition or syndrome associated with disregulation of an endogenous protein affecting ErbB-4 receptor activity, said endogenous protein being at least 50% homologous to at least positions 4-50 of SEQ ID Nos:2 or 15 as determined using the BestFit software of the Wisconsin sequence analysis package, utilizing the Smith and Waterman algorithm, where gap creation penalty equals 8 and gap extension penalty equals 2, the method comprising: 
 (a) obtaining a sample from a subject;    (b) incubating said sample with at least one oligonucleotide or oligonucleotide analog of at least 17 bases, said oligonucleotide or oligonucleotide analog capable of hybridizing to a portion of a polynucleotide strand encoding the endogenous protein, to thereby diagnosing the disease, condition or syndrome associated with disregulation of an endogenous protein affecting ErbB-4 receptor activity.    
     
     
         71 . The method of  claim 70 , wherein said at least one oligonucleotide or oligonucleotide analog comprises a pair of oligonucleotides or analogs specifically hybridizable to said portion of said polynucleotide strand in an opposite orientation so as to direct exponential amplification of at least a portion thereof in a nucleic acid amplification reaction.  
     
     
         72 . The method of  claim 70 , wherein the disease, condition or syndrome is selected from the group consisting of amyotrophic lateral sclerosis (Lou Gehrig's disease), Bell's palsy, spinal muscular atrophy, brain trauma, brain surgery, stroke, brain injury, ischemia, brain and neck malignancies, central nervous system nutritional deficiency, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, Huntington's chorea, Down's syndrome, nerve deafness, Meniere's disease, neuropathy, peripheral neuropathy, hereditary neuropathy, muscular dystrophy, extramammary Paget's disease, gastric cancer, pancreatic cancer, prostate cancer, breast cancer, ovarian cancer, cervical carcinoma, endometrial adenocarcinoma, pancreatic D cells-somatostatinoma and Zollinger-Ellison syndrome.  
     
     
         73 - 74 . (canceled)