An isolated polypeptide (JNK) characterized by having a molecular weight of 46kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.
BACKGROUND OF THE INVENTION
This application is a continuation-in-part application of U.S. Ser. No. 08/220,602, filed Mar. 25, 1994, which is a continuation-in-part application of U.S. Ser. No. 08/094,533 filed Jul. 19, 1993.
The present invention relates to mutations in the MKK4 gene in human cancers and their use in the diagnosis and prognosis of human cancer. Specific mutations in the MKK4 gene which are associated with breast, pancreatic, colorectal and testicular cancers have been identified. The invention also relates to the therapy of human cancers which have a mutation in the MKK4 gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.
A method is disclosed for inhibiting malignant neoplastic growth of epithelial or endothelial cells in a mammal by administering to the mammal an effective amount of an oligonucleotide complementary to at least a portion of mRNA for ERK-1 or ERK-2 that is overexpressed in the mammal. The antisense oligonucleotides are administered to the mammal as a dosage unit. A method of identifying and monitoring potentially malignant neoplastic cell growth in a mammal is also disclosed.
A method is disclosed for inhibiting malignant neoplastic growth of epithelial or endothelial cells in a mammal by administering to the mammal an effective amount of an oligonucleotide complementary to at least a portion of mRNA for ERK-1 or ERK-2 that is overexpressed in the mammal. The antisense oligonucleotides are administered to the mammal as a dosage unit. A method of identifying and monitoring potentially malignant neoplastic cell growth in a mammal is also disclosed.
An isolated polypeptide (JNK characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.
An isolated polypeptide (JNK) characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.