Protein kinase A balances the growth factor‐induced Ras/ERK signaling

FEBS Letters

Jalkanen, Markku¹  Pursiheimo, Juha-Pekka²  Kieksi, Anni²  Salmivirta, Markku¹ 

[1] BioTie Therapies Corp., Tykistökatu 6, 20520 Turku, Finland;Turku Centre for Biotechnology, University of Turku, and Åbo Akademi University, Tykistökatu 6B, BioCity, 20520 Turku, Finland

关键词: Protein kinase A;    Fibroblast growth factor-2;    Growth factor;    Extracellular-regulated kinase;    Raf-1;    Mitogen-activated protein kinase phosphatase-1;    FGF-2;    fibroblast growth factor-2;    EGF;    epidermal growth factor;    PKA;    protein kinase A;    ERK;    extracellular-regulated kinase;    H89;    (N-[2-(p-bromocinnamylamino)-ethyl]-5-isoquinolinesulfonamide);    8-BrcAMP (8-bromoadenosine 3′;    5′-cyclic monophosphate);    MKP-1;    mitogen-activated protein kinase phosphatase-1;    DMEM;    Dulbecco's modified Eagle's medium;    4-OHT;    4-hydroxytamoxifen;    GST;    glutathione S-transferase;   

DOI  :  10.1016/S0014-5793(02)02864-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown