Isolation of a Tumor Promoter Induced C-Fos Kinase
Abstracts
Initial Award Abstract |
C-Fos is a nuclear oncoprotein that can form heterodimers with another nuclear oncoprotein c-Jun, and thus become a part of the
transcription factor AP-1. AP-1 is an important transcriptional regulator that can be activated in response to various mitogenic and
environmental Stimuli like tumor promoter TPA or nicotine. The activation of AP-1 in response to these signals is shown to result
both in increased transcription of its component genes and in the post translational modifications, like phosphorylation of its component proteins.
The objectives of this project were to isolate and characterize the enzyme (protein kinase) that is responsible for the
modification of the transcriptional activator c-Fos by phosphorylating its activation domain. This enzyme was planned
to be used to study its activation in different cell lines and its possible involvement in early events leading to
tracheopulmonar carcinomas.
During this project a Serine/Threonine kinase (JNK2) which belongs to a MAP-kinase subfamily called JNKs or c-Jun N-terminal
kinases was cloned. Careful characterization of this kinase was completed with the help of this fund. This kinase was shown to
be able to phosphorylate c-Jun and an other AP-1 component Jun D in vivo. However we could not show any specificity for this
kinase towards c-Fos. |
Publications
JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation |
Periodical: Genes and Development |
Index Medicus: |
Authors: Kallunki T, Su B, Tsigelny I, et al |
ART |
Yr: 1994 |
Vol: 24 |
Nbr: 8 |
Abs: |
Pg: 2996-3007 |
JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation |
Periodical: Genes and Development |
Index Medicus: |
Authors: Kallunki T, Su B, Tsigelny I, et al |
ART |
Yr: 1994 |
Vol: 24 |
Nbr: 8 |
Abs: |
Pg: 2996-3007 |