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Protein kinase A balances the growth factor‐induced Ras/ERK signaling
Author(s) -
Pursiheimo Juha-Pekka,
Kieksi Anni,
Jalkanen Markku,
Salmivirta Markku
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02864-8
Subject(s) - mapk/erk pathway , protein kinase a , microbiology and biotechnology , mitogen activated protein kinase kinase , signal transduction , c raf , mitogen activated protein kinase 3 , kinase , phosphatase , chemistry , map kinase kinase kinase , protein phosphatase 2 , anti apoptotic ras signalling cascade , biology , phosphorylation
Protein kinase A (PKA) has been proposed to regulate the signal transduction through the Ras/extracellular‐regulated kinase (ERK) pathway. Here we demonstrate that when the PKA activity was inhibited prior to growth factor stimulus the signal flow through the Ras/ERK pathway was significantly increased. Furthermore, the data indicated that this PKA‐mediated regulation was simultaneously targeted to the upstream kinase Raf‐1 and to the ERK‐specific phosphatase mitogen‐activated protein kinase phosphatase‐1 (MKP‐1). Moreover, our data suggested that the level of PKA activity determined the transcription rate of mkp‐1 gene, whereas the Ras/ERK signal was required to protect the MKP‐1 protein against degradation. These results point to a tight regulatory relationship between PKA and the growth factor signaling, and further suggest an important role for basal PKA activity in such regulation. We propose that PKA adjusts the activity of the Ras/ERK pathway and maintains it within a physiologically appropriate level.