Signals generated by the various members of the TGF-beta superfamily mediate a diverse array of biological responses, including immune function, growth control, cell differentiation, sexual reproduction, skeletal formation, and patterning the embryonic body. Yet, unlike what is known for many other cytokines, little is know about the intracellular components in the TGFP signal transduction machinery. Therefore, how cells respond to TGF-beta related ligands remains a central question in the field of developmental and cell biology. In this grant application we plan to focus on understanding the molecular mechanism of mesoderm induction by activin- and BVgl-type TGF-beta growth factors in Xenopus. Specifically, the goals of this research are: (1) to reveal the importance of intracellular antagonism in developing Xenopus embryos; (2) to identify and characterize a transcription factor (AVREBP) that directly mediates activin/BVgl signaling; (3) to determine whether phosphorylation of AVRE-binding protein is important in activin/BVg1 signaling;(4) to investigate the role of Mad - in activin/BVg1 signaling; (5) to identify other intracellular signaling molecules that are components of an activin/BVg1 signaling cascade.
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