title: CREB is activated by UVC through a p38/HOG-1-dependent protein kinase.
abstract: Changes in environmental conditions such as the addition of growth factors or irradiation of cells in culture first affect immediate response genes. We have shown previously that short wavelength UV irradiation (UVC) elicits massive activation of several growth factor receptor-dependent pathways. At the level of the immediate response gene c-fos, these pathways activate the transcription factor complex serum response factor (SRF)-p62TCF which mediates part of the UV-induced transcriptional response. These studies have, however, suggested that more that one pathway is required for full UV responsiveness of c-fos. Using appropriate promoter mutations and dominant-negative cAMP response element (CRE)-binding protein (CREB), we now find that UVC-induced transcriptional activation depends also on the CRE at position -60 of the c-fos promoter and on the functionality of a CREB. Upon UV irradiation, CREB and ATF-1 are phosphorylated at serines 133 and 63, respectively, preceded by and dependent on activation of p38/RK/HOG-1 and of a p38/RK/HOG-1-dependent p108 CREB kinase. Although p90RSK1 and MAPKAP kinase 2 are also activated by UV, p90RSK1 does not, at least not decisively, participate in this signalling pathway to CREB and ATF-1 as it is not p38/RK/HOG-1 dependent, and CREB is a poor substrate for MAPKAP kinase 2 in vitro. On the basis of resistance to the growth factor receptor inhibitor suramin and of several types of cross-refractoriness experiments, the UVC-induced CREB/ATF-1 phosphorylation represents an as yet unrecognized route of UVC-induced signal transduction, independent of suramin-inhibitable growth factor receptors and different from the Erk 1,2-p62TCF pathway.
authors.affiliation: Oregon Health Sciences University, Department of Cell and Developmental Biology, Portland 97201, USA.
authors.forename: M
authors.initials: M
authors.lastname: Iordanov
authors.forename: K
authors.initials: K
authors.lastname: Bender
authors.forename: T
authors.initials: T
authors.lastname: Ade
authors.forename: W
authors.initials: W
authors.lastname: Schmid
authors.forename: C
authors.initials: C
authors.lastname: Sachsenmaier
authors.forename: K
authors.initials: K
authors.lastname: Engel
authors.forename: M
authors.initials: M
authors.lastname: Gaestel
authors.forename: H J
authors.initials: HJ
authors.lastname: Rahmsdorf
authors.forename: P
authors.initials: P
authors.lastname: Herrlich
mesh_terms: D051697:Activating Transcription Factor 1; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D051697:Activating Transcription Factor 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005576:Colforsin; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D010748:Phosphopeptides; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D029701:Saccharomyces cerevisiae Proteins; D013498:Suramin; D014157:Transcription Factors; D000099190:MAP-Kinase-Activated Kinase 2; C088589:HOG1 protein, S cerevisiae