Date of Award

2007

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

Signal transduction involves a signal at the cell's surface being transmitted internally via a chain of molecules to generate an adequate response. Signaling malfunctions are responsible for many human diseases. Signaling mechanisms are conserved in evolution but complexity is brought about by modifications, regulation, multiple-pathways, cross talk between pathways etc. Signaling molecules conserved through evolution are considered basic and indispensable. The stathmin family (Stathmin, SCG10 etc.) belongs to this class of molecules. Stathmin (also known as oncoprotein 18, prosolin, leukemia-associated phosphoprotein 18 and others) is a highly conserved, phosphorylated cytosolic protein with apparent ubiquitous expression. Stathmin protein is encoded by a gene present in humans at the locus 1p36.1-p35. Stathmin binds and sequesters tubulin and thus plays a role in microtubule dynamics. Although its other functions are unknown it is a messenger protein that may participate in both general and specific regulatory pathways. Superior cervical ganglion-10 is a membrane-associated protein that shares significant amino acid sequence similarity with stathmin. SCG10 is a neuronal growth-associated protein encoded by a gene present in humans at the locus 8q 13.2. Although a few Stathmin/SCG10 interacting molecules (e.g. Tubulin, Hsc70, Tsg101 etc.) have been identified, the mechanism and effect on subsequent signaling pathways remain un-delineated. To delineate this, it is imperative to broaden our database of Stathmin/SCG10-binding proteins. To identify binding proteins we used in vitro 'GST-Stathmin pull down assays' and in vivo Yeast two hybrid screening. Our in vitro study identified Hsp70 as a stathmin-binding protein. We also show that phosphorylation of p38 (α) kinase is involved in Prolactin-induced proliferation of Nb2 cells. Our yeast two hybrid screen identified five novel Stathmin binding proteins, three new SCG10 binding proteins and a putative brain transcription factor that greatly increases yeast mating.

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