Authors

Arif Kirmizitas

Type

Text

Type

Thesis

Date

2008-12-01

Keywords

Transforming Growth Factor | signaling proteins | GTPBP2 | Xenopus embryos

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/70833

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

The Transforming Growth Factor(TGF-) superfamily of signaling proteins regulate a diverse set of biological processes, including cell proliferation, adhesion, migration, apoptosis, differentiation and embryonic pattern formation. Because of its key role in these processes, a plethora of regulators are evolved to modulate TGF- signaling. The TGF- superfamily is comprised of about 30 ligands, which are commonly grouped into two broad sub-families based on their downstream signaling effectors: the TGF- /Nodal/Activin and BMP/GDF families. To identify novel molecules that regulate the intracellular BMP/Smad1 signaling pathway, we have undertaken a yeast two-hybrid screen using Smad1, and retrieved GTPBP2 as a binding partner for Smad1. GTPBP2 and its close homolog GTPBP1 are large GTPases of unknown function. In this study, I have shown that GTPBP2 interacts with a subset of Smad proteins, and consistent with these interactions GTPBP2 induces mesoderm in explants and enhances canonical TGF signaling pathways in Xenopus and HepG2 cells. GTPBP2 mRNA is maternal and expressed in a dynamic pattern in developing Xenopus embryos. By knocking down GTPBP2 levels, I showed that GTPBP2 is required for mesendodermal patterning, and BMP signaling. GTPBP2 is a nuclear protein and colocalizes to nuclear foci with Smad1. In conclusion, these results show that GTPBP2 is a positive regulator of TGF- signaling.

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