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Isolation of a Tumor Promoter Induced C-Fos Kinase

Institution: University of California, San Diego
Investigator(s): Tuula Kallunki, Ph.D.
Award Cycle: 1995 (Cycle 4) Grant #: 4FT-0105 Award: $55,000
Subject Area: Cancer
Award Type: Postdoctoral Fellowship Awards
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