Regulation of the Golgi Apparatus by p38 and JNK Kinases during Cellular Stress Responses

• Published in: International journal of molecular sciences 2021-09, Vol.22 (17), p.9595
• Main Authors: Nordgaard, Cathrine, Tollenaere, Maxim A X, Val, Ana Martinez Del, Bekker-Jensen, Dorte B, Blasius, Melanie, Olsen, Jesper V, Bekker-Jensen, Simon
• Format: Article
• Language: English
• Subjects: c-Jun protein; Carrier Proteins - metabolism; Cell cycle; Cell division; Cell Line, Tumor; Cellular stress response; Cyclin-dependent kinases; Cytokines; Gene regulation; GIGYF; Golgi apparatus; Golgi Apparatus - metabolism; Humans; Immune system; Inflammation; JNK; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; MAP kinase; MAP Kinase Kinase 4 - metabolism; MAP Kinase Kinase 4 - physiology; MAP Kinase Signaling System - physiology; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - metabolism; p38; p38 Mitogen-Activated Protein Kinases - metabolism; p38 Mitogen-Activated Protein Kinases - physiology; Phosphorylation; Physiology; Principal components analysis; Protein kinase; Proteins; Proteomics; Proto-Oncogene Proteins c-jun - metabolism; Signal Transduction; stress signaling; Stress, Physiological - physiology; Transcription factors; translation and Golgi
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22179595

p38 and c-Jun N-terninal kinase (JNK) are activated in response to acute stress and inflammatory signals. Through modification of a plethora of substrates, these kinases profoundly re-shape cellular physiology for the optimal response to a harmful environment and/or an inflammatory state. Here, we utilized phospho-proteomics to identify several hundred substrates for both kinases. Our results indicate that the scale of signaling from p38 and JNK are of a similar magnitude. Among the many new targets, we highlight the regulation of the transcriptional regulators grb10-interacting GYF protein 1 and 2 (GIGYF1/2) by p38-dependent MAP kinase-activated protein kinase 2 (MK2) phosphorylation and 14-3-3 binding. We also show that the Golgi apparatus contains numerous substrates, and is a major target for regulation by p38 and JNK. When activated, these kinases mediate structural rearrangement of the Golgi apparatus, which positively affects protein flux through the secretory system. Our work expands on our knowledge about p38 and JNK signaling with important biological ramifications.