FUNCTIONAL DIFFERENCES BETWEEN STAT3-ALPHA AND STAT3-BETA

Stat3 beta is a short form of Stat3 that differs from the longer form (Stat3 alpha) by the replacement of the C-terminal 55 amino acid resid ues of Stat3 alpha by 7 residues specific to Stat3 beta. In COS cells transfected with Stat3 expression plasmids, both Stat3 alpha and Stat3 beta were activated for DNA binding and transcription by the same set of growth factors and cytokines and both, when activated, formed homo dimers and heterodimers with Stat1. Only Stat3 beta was active in the absence of added cytokine or growth factor, Activation of each form, i ncluding constitutive activation of Stat3 beta, was correlated with th e phosphorylation of tyrosine 705. Activated Stat3 beta in transfected COS cells was more stable and had greater DNA-binding activity than a ctivated Stat3 alpha. However, relative to DNA-binding activity, Stat3 alpha showed greater transcriptional activity than Stat3 beta. A muta nt of Stat3 alpha lacking its highly acidic C-terminal 48 amino acids had properties indistinguishable from Stat3 beta. we conclude that Sta t3 alpha and Stat3 beta have significantly different properties due to the presence or absence of the acidic C-terminal tail of Stat3 alpha rather than the C-terminal sequence peculiar to Stat3 beta. In additio n to its effect on transcription, we speculate that the acidic tail ma y destabilize the active dimeric form of Stat3 alpha, resulting in low er DNA-binding activity of the Y705-phosphorylated form compared to St at3 beta and in more rapid dephosphorylation.