DIFFERENTIAL ACTIVATION OF TRANSCRIPTION FACTORS INDUCED BY CA2+ RESPONSE AMPLITUDE AND DURATION

Citation
Re. Dolmetsch et al., DIFFERENTIAL ACTIVATION OF TRANSCRIPTION FACTORS INDUCED BY CA2+ RESPONSE AMPLITUDE AND DURATION, Nature, 386(6627), 1997, pp. 855-858
Citations number
30
Categorie Soggetti
Multidisciplinary Sciences
Journal title
NatureACNP
ISSN journal
00280836
Volume
386
Issue
6627
Year of publication
1997
Pages
855 - 858
Database
ISI
SICI code
0028-0836(1997)386:6627<855:DAOTFI>2.0.ZU;2-3
Abstract
An increase in the intracellular calcium ion concentration ([Ca2+](i)) controls a diverse range of cell functions, including adhesion, motil ity, gene expression and proliferation(1,2). Calcium signalling patter ns can occur as single transients, repetitive oscillations or sustaine d plateaux(2,3), but it is not known whether these patterns are respon sible for encoding the specificity of cellular responses. We report he re that the amplitude and duration of calcium signals in B lymphocytes controls differential activation of the pro-inflammatory transcriptio nal regulators NF-kappa B, c-Jun N-terminal kinase (JNK) and NFAT. NF- kappa B and JNK are selectively activated by a large transient [Ca2+]( i) rise, whereas NFAT is activated by a low sustained Ca2+ plateau. Di fferential activation results from differences in the Ca2+ sensitiviti es and kinetic behaviour of the three pathways. Our results show how d ownstream effecters can decode information contained in the amplitude and duration of Ca2+ signals, revealing a mechanism by which a multifu nctional second messenger such as Ca2+ can achieve specificity in sign alling to the nucleus.