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Transcriptional profiling defines the roles of ERK and p38 kinases in epidermal keratinocytes
Author(s) -
Gazel Alix,
Nijhawan Rajiv I.,
Walsh Rebecca,
Blumenberg Miroslav
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21394
Subject(s) - mapk/erk pathway , biology , microbiology and biotechnology , signal transduction , kinase , transcription factor , gene expression profiling , p38 mitogen activated protein kinases , gene expression , gene , genetics
Abstract Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change gene expression. Using pathway‐specific transcriptional profiling, we identified the genes regulated by two such pathways, p38 and ERK. These pathways are at the fulcrum of epidermal differentiation, proliferative and inflammatory skin diseases. We used SB203580 and PD98059 as specific inhibitors and Affymetrix Hu133Av2 microarrays, to identify the genes regulated after 1, 4, 24, and 48 h and compared them to genes regulated by JNK. Unexpectedly, inhibition of MAPK pathways is compensated by activation of the NFκB pathway and suppression of the DUSP enzymes. Both pathways promote epidermal differentiation; however, there is a surprising disconnect between the expression of steroid synthesis enzymes and differentiation markers. The p38 pathway induces the expression of extracellular matrix and proliferation‐associated genes, while suppressing microtubule‐associated genes. The ERK pathway induces nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Transcription factors SRY, c‐FOS, and N‐Myc are the principal targets of the p38 pathway, Elk‐1 SAP1 and HLH2 of ERK, while FREAC‐4, ARNT and USF are shared. The results suggest a list of targets potentially useful in therapeutic interventions in cutaneous diseases and wound healing. J. Cell. Physiol. 215: 292–308, 2008. © 2008 Wiley‐Liss, Inc.