Dictyostelium kinase DPYK3 negatively regulates STATc signaling in cell fate decision.

DPYK3, a member of the Dictyostelium TKL (tyrosine kinase like) kinase family, was ablated by homologous recombination. dpyk3- cells displayed aberrant pattern formation during development. The prestalk O zone was not properly formed and, instead, the prespore zone was expanded in dpyk3- slugs. During development, the transcription factor STATc (signal transducers and activators of transcription c) was persistently phosphorylated and ecmAO expression level was kept low in dpyk3- cells. Furthermore, in response to differentiation inducing factor-1 (DIF-1) in suspension culture, dpyk3- cells displayed persistent STATc phosphorylation and reintroduction of DPYK3 in dpyk3- cells restored transient STATc phosphorylation similarly to wild type cells. In contrast to the positive STAT regulation by Janus Kinase in metazoans, Dictyostelium DPYK3 negatively regulates STATc during development in response to DIF-1 signaling.