Interaction Between Vangl2 And Scrib1 And Screening Brain Library With Vangl2 By Means Of Yeast Two-hybrid Technique

Vangl2(van Gogh-like,formerly "loop-tail associated protein Ltap") is a 521-amnio acid transmembrane(TM) protein composed of four putative domains in the N-terminal half .The Oterminal half is predicted to be cytoplasmic and is possibly involved in intracellular signaling and/or interaction with other protein .Vangl2 is a component of non-canonical WNT signaling pathway,Vangl2 protein plays a key developmental role in establishing planar cell polarity.It regulates the cell orientation .Now it has been identified that vangl2 ,as the gene mutated in the mouse model of severe NTD(neural tub defect) ,known as looptail (Lp).loop-tail (Lp) mutant mouse ..provides a model for the most severe NTD,craniorachischisis,in which the brain and spinal cord remain open .morphological analysis of the Lp mice shows that the defect results from an abnormally broad floor plate ,most likely through a failure in convergent extension.Scrib1 is a gene that can restrain cancer. It is reported that the mutation of scrib1 can lead the epithelia cell polarity abnormal and over-growth in drosophila. The mutation of scrib1 also was found to be related to the circle-tail phenotype in mice, and these mice also have NTD. These phenomenons tell us maybe vangl2 and scrib1 play roles in the same signal pathway.In this study, we demonstrate scrib1 and vangl2 have interactions. By means of yeast two hybrid technique, we contracted a plasmid containing c-fragment of vangl2 to screen embryonic brain library and we found the non-receptor protein tyrosine phosphatase (PTPN18) associates with vangl2. Protein tyrosine phosphatase is closely related to cancer, and it controls the phosphorylation of many proteins. In WNT signaling pathway, WNT activates Fz, Fz mediate phosphorylation of Dsh, phosphorylated Dsh repress GSk-3(3, lead P-catenin accumulates, which regulates many gene transcription. Like Fz, vangl2 is also a trans-membrane protein, and we found it can interact with both PTPN18 and scrib1. Our lab reported that scribl interacts with praline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), and we know PSTPIP1 has interaction with PTPN18 by consult the database on www.bind.ac. So we can predict that when stimulated by extracellular signals vangl2 can form vangl2-ptpn18-pstpip1-scrib1 complex, leading to some downstream molecule phosphorylation or de phosphorylation and transferring the signal into the cell.