Screening Interactive Protein Of STK11 C-terminal By Yeast Two-Hybrid

Peutz-Jeghers syndrome(OMIM,175200), which is an autosomal dominant genetic disease, has a prevalence of approximately 1 in 8,300 to 28,000 births. This disease is characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa, so it was also called The Mole Polyps Syndrome. Another character is its high incidence of malignancy among these patients, so much attention was focused on this gene. At present, the only identified pathogenic gene is STK11 (also known as LKBl), STK11/LKB1 gene is located on chromosome 19p13.3 and spans 23 kb genomic region, it contains 10 exons and 11 introns, its full length cDNA is 2185bps and the coding region is 1302bps. The STK11/LKB1 gene, which encodes a member of the serine/threonine kinase, regulates cell polarity, embryonic development and other important physiological functions. STK11/LKB1 gene can suppress tumor cell proliferation and maintain energy homeostatsis, STK11/LKB1 exerts these effects through crosstalking with p53, wnt and AMPK signaling system. The expression of STK11/LKB1 is regulated in a temporal-spatial specific manner.Although the primary cause of the PJS development in the patients is mutations of the catalytic domain of STK11/LKB1 gene that lead to the loss of serine/threonine kinase activity, mutations that affect only carboxyl terminal region of STK11/LKB1 have also been identified in PJS patients as well as in other tumors. The C-terminal non-catalytic region of the STK11/LKB1 protein is encoded by exon 8 and 9 and encompasses amino acids 309-433. The C-terminal region of STK11/LKB1 contains several post-translational modification sites. A prenylation motif as well as 5 phosphorylation sites have been identified:two residues are autophosphorylation sites (Thr336 and Thr402) and three others (Ser325, Thr363, Ser428) are phosphorylated by upstream kinases. Overexpression of STK11/LKB1 C-terminal can interfere with the function of STK11/LKB1, these findings reveal a crucial regulatory role of the STK11/LKB1 C-terminal region, this region may exert its effect through interacting with downstream proteins, and mutations in this region disrupt the interactions.We use the MatchmakerTM Gold Yeast Two-Hybrid System and screen the interaction protein of the STK11/ LKB1 C-terminal region----PGM1(phosphoglucomutase 1),the results may shed light on the function of STK11/LKB1 C-terminal.