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

• Published in: International journal of molecular sciences Vol. 22; no. 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: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.09.2021; MDPI
• Subjects: Carrier Proteins - metabolism; Cell cycle; Cell division; Cell Line, Tumor; Cyclin-dependent kinases; Cytokines; Golgi Apparatus - metabolism; Humans; Immune system; Inflammation; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; 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 Mitogen-Activated Protein Kinases - metabolism; p38 Mitogen-Activated Protein Kinases - physiology; Phosphorylation; Physiology; Principal components analysis; Proteins; Proto-Oncogene Proteins c-jun - metabolism; Signal Transduction; Stress, Physiological - physiology; GIGYF; translation and Golgi; p38; phosphorylation; JNK; stress signaling
• 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.