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The Dictyostelium Prestalk Inducer DIF-1 Directs Phosphorylation of a bZIP Transcription Factor

The Dictyostelium Prestalk Inducer DIF-1 Directs Phosphorylation of a bZIP Transcription Factor

Yoko Yamada, Yuzuru Kubohara, Haruhisa Kikuchi, Yoshiteru Oshima, Hong-Yu Wang, Susan Ross, Jeffrey G Williams

Int J Dev Biol. 2013;57(5):375-81.

PMID: 23873369

Abstract:

DIF-1, a chlorinated hexaphenone produced by developing Dictyostelium cells, induces prestalk differentiation. DimB is a bZIP transcription factor that accumulates in the nucleus upon exposure to DIF-1, where it directly activates transcription of DIF-responsive genes. The signaling steps upstream of DimB and downstream of DIF-1 are entirely unknown. Analysis by mass spectrometry shows that incubation with DIF-1 rapidly stimulates phosphorylation at several sites in DimB. We characterize the most highly responsive site, S590, which is located very close to the C terminus. A point mutation in this site, S590A, does not inhibit DimB nuclear accumulation in response to DIF. However, this seems likely to reflect functional redundancy with other sites; because a panel of chemical variants on the structure of DIF-1 show a correlation between their potencies as inducers of DimB nuclear accumulation and their potencies as inducers of phosphorylation at S590. Furthermore, the S590A mutant is fully active in mutant rescue of a dimB null strain, arguing against an alternative role in transcriptional activation of target genes. We conclude that i) DIF-1 directs phosphorylation at S590, ii) although it is not essential for nuclear accumulation in response to DIF-1 correlative evidence, based upon a panel of DIF-1 related molecules, suggests that this modification may play a redundant role in the process. iii) We also present evidence that the kinase activity, which phosphorylates S590, is non-nuclear and that this signalling pathway is, in part at least, independent of the DIF-regulated STATc activation pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP111050727	DIF-1		111050-72-7	Price

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