Use of human Biliverdin reductase and fragments thereof protein kinase C-δ and ERK related conditions
The present invention is directed to methods of modulating PKC-δ activity and PKC-δ/ERK complex activity in cells via biliverdin reductase. Methods and compositions for diagnosing and treating a PKC-δ and PKC-δ/ERK complex related condition are also disclosed.
1. A method of modulating PKC-δ activity in a population of cells, said method comprising:
administering to the population of cells a mammalian biliverdin reductase (BVR) peptide fragment that inhibits PKC-δ activity, the peptide fragment consisting of the amino acid sequence of FXFPXF[S/T]G (SEQ ID NO: 33), wherein X at amino acid positions 2 and 5 is any amino acid, under conditions effective to modulate PKC-δ activity in the population of cells.
2. The method according to claim 1 , wherein the agent modulates PKC-δ/ERK complex formation and/or activity in the population of cells.
3. The method according to claim 1 , wherein the population of cells is selected from the group consisting of a population of mammalian cancer cells, neuronal cells, cardiocytes, leukocytes, and fibroblasts.
4. A method of treating a PKC-δ related condition in a subject comprising:
administering to the subject having the PKC-δ related condition a mammalian biliverdin reductase (BVR) peptide fragment that inhibits PKC-δ activity, the peptide fragment consisting of the amino acid sequence of FXFPXF[S/T]G (SEQ ID NO: 33), wherein X at amino acid positions 2 and 5 is any amino acid, under conditions effective to treat the PKC-δ related condition.
5. The method according to claim 4 , wherein the PKC-δ related condition involves PKC-δ/ERK complex formation and/or activity.
6. The method according to claim 4 , wherein the PKC-d related condition is characterized by a reduction in PKC-d activity and is selected from the group consisting of an autoimmune disorder, inflammatory disease, and cytostasis.
7. The method according to claim 4 , wherein the PKC-δ related condition is characterized by an increase in PKC-δ activity and is selected from the group consisting of neurodegeneration, cancer, ischemia, inflammation, diabetes, atherogenesis, myocardial infarction, and an autoimmune disorder.
8. The method according to claim 7 , wherein the PKC-δ related condition is cancer and is selected from the group consisting of colon cancer, prostate cancer, and head and neck carcinoma.
9. The method of claim 1 , wherein the agent modulates NF-kappaB activity.
10. The method of claim 4 , wherein the agent modulates NF-kappaB activity.