Tubby Signaling Pathway

The tubby gene product is expressed in the brain and has been implicated by mouse genetics in obesity and other disorders such as blindness. Structural analysis predicts that this gene acts as a transcription factor, binding to DNA to regulate gene expression. More recently, it was reported that tubby binds to phosphoinositides in the plasma membrane, helping to localize this factor in the membrane region in the absence of pathway activation. Tubby also interacts with Gq-alpha g-protein subunits, localizing tubby to regions of g-protein activation. Activation of phosphatase C activity and hydrolysis of membrane phosphoinositides leads to release of tubby from the plasma membrane, allowing tubby to enter the nucleus to bind DNA and regulate transcription. Some G-protein coupled receptors such as 5-HT2c may signal in part through tubby in addition to calcium-mediated pathways and protein-kinase signaling pathways. The identity of genes regulated by tubby and the mechanism by which tubby affects obesity remain to be explored. (NCI Thesaurus/BIOCARTA)

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