Novel Secretory Protein MLeg1 Function As A New Regulator Of Akt Signaling Through Binding To EGFR

Leg1 is a novel secretory protein conserved throughout the vertebrate kingdom. Due to the fact that no information is available regarding Legl’s targeting tissues/organs and that Legl protein sequence contains only a function unknown domain 781 (DUF781), it is a big challenge to study Legl’s function. Until now, there is no any report on studying legl homologous gene in mouse(mleg1). In this thesis, by using the Cre-loxP system, we generated the mlegl knockout mouse (mleg1△/△) and carried out an in depth study of the function of mLegl.We found that mlegl is mainly expressed in the salivary glands in mouse, and the protein is secreted into the saliva. Along with the saliva, mLegl enters the digestive system, and is then absorbed and enters the blood circulation. Finally, it arrives in the liver and binds to EGFR, so that to activate the EGFR/PI3K/Akt signalling pathway, and to regulate liver’s function. Our study not only sheds light on the biological role of mLegl but also reveals how salivary glands regulates liver function. Our findings define a novel signalling pathway, starting from mLegl to EGFR, PI3K, and finally regulating the Akt activity.In addition, we found that starvation induced the expression of mlegl, and this starvation induced leg1 expression is also conserved in zebrafish. This induced mLegl help to maintain Akt phosphorylation level so that to prevent the accumulation of p53 and protect the hepatocytes under starvation.All together, our work made a breakthrough in mLegl that will no doubt guide our future research about the biological and physiological functions of mLeg1 under different growth conditions.