XB-ART-5203Mech Dev May 1, 2003; 120 (5): 629-37.
Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling.
Tob inhibits bone morphogenetic protein (BMP) signaling by interacting with receptor-regulated Smads in osteoblasts. Here we provide evidence that Tob also interacts with the inhibitory Smads 6 and 7. A yeast two-hybrid screen identified Smad6 as a protein interacting with Tob. Tob co-localizes with Smad6 at the plasma membrane and enhances the interaction between Smad6 and activated BMP type I receptors. Furthermore, we have isolated Xenopus Tob2, and show that it cooperates with Smad6 in inducing secondary axes when expressed in early Xenopus embryos. Finally, Tob and Tob2 cooperate with Smad6 to inhibit endogenous BMP signaling in Xenopus embryonic explants and in cultured mammalian cells. Our results provide both in vitro and in vivo evidence that Tob inhibits endogenous BMP signaling by facilitating inhibitory Smad functions.
PubMed ID: 12782279
Article link: Mech Dev
Genes referenced: smad6 smad6.2 tob2
Article Images: [+] show captions
|Fig. 3. Expression of Xenopus Tob2 in early Xenopus embryos. (A) Northern blot analysis of XTob2 expression in normal Xenopus embryos. There was an XTob2 transcript of about 5.5 kb expressed maternally and throughout early Xenopus development (closed arrow). An additional, larger transcript of about 7.5 kb was detected by the late gastrula stage (open arrow). Src is used as a loading control. (B–D) Whole mount in situ hybridization analysis of XTob2 expression in early Xenopus embryos. (B) Lateral view of a gastrula (stage 10.5) embryo; the animal pole is up. XTob2 is expressed ubiquitously in the animal region of the embryo. Arrowhead, dorsal blastopore lip. (C) Dorsolateral view of a late gastrula (Stage 12.5) embryo; anterior is to the left, dorsal is up. (D) Lateral view of a tailbud stage embryo (stage 30/31). Note that there is elevated expression in several areas: the anterior ventral blood islands (black arrow), somites (white arrow), otic vesicle, eyes, brain, branchial arches and the heart anlage.|