Tubby is an autosomal recessive syndrome characterized by maturity-obesity, insulin resistance, infertility, and cochlear and retinal
degeneration. Tubby protein (Tub) is highly expressed in brain, especially hypothalamus where body weight regulation is controlled. The
sequence of normal tubby includes putative tyrosine phosphorylation sites for SH-2 protein binding and a nuclear localization signal (NLS),
while mutant tubby contains a 24 intron amino-acid insert substituted for 44 C-terminal amino acids. In PC12 cells, insulin induces tyrosine
phosphorylation. In vitro, tubby is phosphorylated by insulin receptor kinase, Abl, JAK2, and upon phosphorylation tubby associates with the
SH2 domains of Abl, Lck, phospholipase Cγ. The C-terminal region of tubby binds to phosphatidylinositol 4,5-bis-phosphate, which
facilitates localization to the plasma membrane. Receptor-mediated activation of Gαq releases tubby from the plasma membrane through the
action of phospholipase C-B. This allows translocation of tubby to the nucleus where it may regulate transcription. Thus, tubby is a
transcription regulator activated by the G-protein phospholipid signaling pathway.
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注意事项:
1.Since applications vary, each investigator should titrate the reagent to obtain optimal results.
2.Caution: Sodium azide yields highly toxic hydrazoic acid under acidic conditions. Dilute azide compounds in running water before discarding to avoid accumulation of potentially explosive deposits in plumbing.