Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain.
The mitogen-activated protein kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs), are a group of serine/threonine terminal protein kinases activated downstream of a pleiotrophy of transmembrane receptors. Main intracellular components of the MAPK signalling pathway are the RAF, MEK, and ERK proteins, which work in a cascade of activator and effector proteins. They regulate many fundamental cellular functions, including cell proliferation, cell survival, and cell differentiation by transducing extracellular signals to cytoplasmic and nuclear effectors. To reveal more details about possible activation cascades in this pathway, the present study gives a complete description of the differential expression of Braf, Mek1, Mek2, Mek5, Erk1, Erk2, Erk3, and Erk5 in the adult murine brain by way of in situ hybridization analysis. In this study, we found that each gene is widely expressed in the whole brain, except for Mek2, but each displays a very distinct expression pattern, leading to distinct interactions of the MAPK components within different regions. Most notably we found that 1) Braf and Erk3 are coexpressed in the hippocampus proper, confirming a possible functional interaction; 2) in most forebrain areas, Mek5 and Erk5 are coexpressed; and 3) in the neurogenic regions of the brain, namely, the olfactory bulb and the dentate gyrus, Braf is absent, indicating that other activator proteins have to take over its function. Despite these differences, our results show widespread coexpression of the pathway components, thereby confirming the hypothesis of redundant functions among several MEK and ERK proteins in some regions of the brain.
Di Benedetto
Barbara
B
GSF National Research Center for Environment and Health, Institute of Developmental Genetics, 85764 Neuherberg, Germany.
Hitz
Christiane
C
Hölter
Sabine M
SM
Kühn
Ralf
R
Vogt Weisenhorn
Daniela M
DM
Wurst
Wolfgang
W
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology*; D018891:Dentate Gyrus / Q000033:anatomy & histology / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000033:anatomy & histology / Q000201:enzymology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*
D012333:RNA, Messenger; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases