TY  - JOUR
AU  - Farhan, Hesso
AU  - Wendeler, Markus W
AU  - Mitrovic, Sandra
AU  - Fava, Eugenio
AU  - Silberberg, Yael
AU  - Sharan, Roded
AU  - Zerial, Marino
AU  - Hauri, Hans-Peter
TI  - MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening.
JO  - The journal of cell biology
VL  - 189
IS  - 6
SN  - 1540-8140
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DZNE-2020-07647
SP  - 997-1011
PY  - 2010
AB  - To what extent the secretory pathway is regulated by cellular signaling is unknown. In this study, we used RNA interference to explore the function of human kinases and phosphatases in controlling the organization of and trafficking within the secretory pathway. We identified 122 kinases/phosphatases that affect endoplasmic reticulum (ER) export, ER exit sites (ERESs), and/or the Golgi apparatus. Numerous kinases/phosphatases regulate the number of ERESs and ER to Golgi protein trafficking. Among the pathways identified, the Raf-MEK (MAPK/ERK [extracellular signal-regulated kinase] kinase)-ERK cascade, including its regulatory proteins CNK1 (connector enhancer of the kinase suppressor of Ras-1) and neurofibromin, controls the number of ERESs via ERK2, which targets Sec16, a key regulator of ERESs and COPII (coat protein II) vesicle biogenesis. Our analysis reveals an unanticipated complexity of kinase/phosphatase-mediated regulation of the secretory pathway, uncovering a link between growth factor signaling and ER export.
KW  - Animals
KW  - COP-Coated Vesicles: metabolism
KW  - Databases, Factual
KW  - Endoplasmic Reticulum: metabolism
KW  - Fluorescence Recovery After Photobleaching
KW  - Golgi Apparatus: metabolism
KW  - HeLa Cells
KW  - Humans
KW  - MAP Kinase Signaling System: physiology
KW  - Mannose-Binding Lectins: genetics
KW  - Mannose-Binding Lectins: metabolism
KW  - Membrane Proteins: genetics
KW  - Membrane Proteins: metabolism
KW  - Mitogen-Activated Protein Kinases: genetics
KW  - Mitogen-Activated Protein Kinases: metabolism
KW  - Phosphoric Monoester Hydrolases: metabolism
KW  - Phosphotransferases: metabolism
KW  - RNA Interference
KW  - RNA, Small Interfering: genetics
KW  - RNA, Small Interfering: metabolism
KW  - Secretory Pathway: physiology
KW  - Vesicular Transport Proteins: genetics
KW  - Vesicular Transport Proteins: metabolism
KW  - LMAN1 protein, human (NLM Chemicals)
KW  - Mannose-Binding Lectins (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - RNA, Small Interfering (NLM Chemicals)
KW  - Vesicular Transport Proteins (NLM Chemicals)
KW  - Phosphotransferases (NLM Chemicals)
KW  - Mitogen-Activated Protein Kinases (NLM Chemicals)
KW  - Phosphoric Monoester Hydrolases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:20548102
C2  - pmc:PMC2886346
DO  - DOI:10.1083/jcb.200912082
UR  - https://pub.dzne.de/record/141325
ER  -