Dynamic Microtubules Required for STAT5b

Abstract

Activation of the STAT (signal transducer and activator of transcription) family of transcription factors involves transport to the nucleus from cytosolic pools. Phung-Koskas et al. report that microtubules are required for the translocation of STAT5b, but not other STAT proteins, in the WIF-B hepatic cell line. When microtubules were destabilized with nocodazole prior to stimulation of the cells with the cytokine growth hormone (GH), nuclear accumulation of STAT5b, but not that of STAT3, was decreased. Phosphorylation of STAT5b was not affected by nocodazole. A direct interaction with microtubules was indicated by sedimentation of a fraction of STAT5b selectively with microtubules and by colocalization in immunofluorescence experiments. Stabilization of microtubules with taxol inhibited the interaction of STAT5b with the microtubules and decreased the nuclear translocation of STAT5b in response to GH. Furthermore, STAT5b associated only with dynamic microtubules in assays designed to separate the dynamic from the stable microtubule network or to selectively inhibit the dynamic microtubule network. Thus, STAT5b appears to interact specifically with dynamic microtubules. Both cytosolic and microtubule-associated STAT5b were phosphorylated in response to GH; however, the microtubule-associated pool decreased over time, suggesting that phosphorylation triggers the release of STAT5b from the microtubules. When the microtubule motor dynein was inhibited by overexpression of dynamitin, the transport of STAT5b to the nucleus was decreased, suggesting that active transport along the dynamic microtubule network is involved in translocation of STAT5b to the nucleus. T. Phung-Koskas, A. Pilon, C. Poüs, C. Betzina, M. Sturm, M.-L. Bourguet-Kondracki, G. Durand, A. Drechou, STAT5B-mediated growth hormone signaling is organized by highly dynamic microtubules in hepatic cells. J. Biol. Chem. 280 , 1123-1131 (2005). [Abstract] [Full Text]