Re. Dolmetsch et al., DIFFERENTIAL ACTIVATION OF TRANSCRIPTION FACTORS INDUCED BY CA2+ RESPONSE AMPLITUDE AND DURATION, Nature, 386(6627), 1997, pp. 855-858
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.