Abstract: The present invention relates to methods and compositions for the specific inhibition of kinase suppressor of Ras (KSR). In particular, the invention provides genetic approaches and nucleic acids for the specific inhibition of KSR, particularly of KSR expression. The invention relates to antisense oligonucleotides and the expression of nucleic acid which is substantially complementary to KSR RNA. Oligonucleotide and nucleic acid compositions are provided. The invention provides methods to inhibit KSR, including inhibition of KSR expression. Methods for blocking gƒ Ras mediated tumorigenesis, metastasis, and for cancer therapy are provided. Methods for conferring radiosensitivity to cells are also provided.

Abstract: Described are methods for protecting the female reproductive system against natural and artificial insults by administering to women a composition comprising an agent that antagonizes one or more acid sphingomyelinase (ASMase) gene products. Specifically, methods disclosed herein serve to protect women's germline from damage resulting from cancer therapy regimens including chemotherapy or radiotherapy. In one aspect, the method preserves, enhances, or revives ovarian function in women, by administering to women a composition containing sphingosine-1-phosphate, or an analog thereof. Also disclosed are methods to prevent or ameliorate menopausal syndromes and to improve in vitro fertilization techniques.

Abstract: Described are methods for protecting the female reproductive system against natural and artificial insults by administering to women a composition comprising an agent that antagonizes one or more acid sphingomyelinase (ASMase) gene products. Specifically, methods disclosed herein serve to protect women's germline from damage resulting from cancer therapy regimens including chemotherapy or radiotherapy. In one aspect, the method preserves, enhances, or revives ovarian function in women, by administering to women a composition containing sphingosine-1-phosphate, or an analog thereof. Also disclosed are methods to prevent or ameliorate menopausal syndromes and to improve in vitro fertilization techniques.

Abstract: The subject invention provides a purified membrane-bound ceramide-activated protein kinase having an apparent molecular weight of about 110 kD as determined by SDS polyacrylamide gel electrophoresis, which protein kinase is capable of specifically phosphorylating the threonine residue in a Thr-Pro- or a Thr-Leu-Pro-containing polypeptide. The subject invention also provides a method of determining whether an agent is capable of specifically inhibiting the phosphorylation activity of the ceramide-activated protein kinase. The subject invention further provides a method of determining whether an agent is capable of specifically stimulating the phosphorylation activity of the ceramide-activated protein kinase. The subject invention further provides a method of treating a subject having an inflammatory disorder. The subject invention further provides a method of treating a human subject infected with HIV so as to reduce the proliferation of HIV in the human subject.

Abstract: A membrane-bound ceramide-activated protein kinase has been purified from human cells. The protein kinase has an apparent molecular weight of about 95 kD and specifically phosphorylates the threonine residue in a polypeptide containing Pro-Leu-Thr-Pro (SEQID NO:1).