MPA2 | |
Project ID | MPA2 [Protein] |
Project Theme | Drug discovery-oriented analysis for structure and function of DOCK2 signaling molecules |
Project Theme (short) | DOCK2 signaling molecules |
Principal Investigator | Yoshinori Fukui |
Affiliation | Medical Institute of Bioregulation, Kyushu University |
Backgrounds | - While immunity is our indispensable defense system, excessive immune responses cause diseases such as autoimmune diseases - Rac family proteins regulate a diverse array of immune cellular events including cell migration - We found DOCK2 protein to be a master regulator of the Rac activation in immune cells - Inhibition of signal transduction from DOCK2 to Rac could lead to the repression of inappropriate immune responses |
Highlights | - The structures of N-terminal domain of DOCK2 in complex with ELMO1 protein have been determined. The structural analysis of the full length DOCK2 is in progress - Compounds that inhibit DOCK2 signal transduction have been identified - Involvements of DOCK2 in the type I interferon production and the regulation of allergic response have been elucidated - We revealed that intracellular DOCK2 dynamics were sequentially regulated by two distinct phospholipids during neutrophil chemotaxis |
Outline | Immune cells are moving around our body to respond immediately to infection. We discovered a protein DOCK2 which is expressed in lymphocytes and regulates their migration. The first signal to trigger the migration of immune cells like lymphocytes is brought by binding of extracellular chemokine to chemokine receptors on the cell membrane of leukocytes. This stimulation is successively transmitted to various factors and activates a small G protein Rac which in turn reorganizes actin filaments, resulting in the migration of cells. DOCK2 is indispensable for the Rac activation. We found that transplanted hearts of mice lacking DOCK2 are stably engrafted without immunosuppressants. Therefore, compounds that inhibit the activity of DOCK2 and thereby block the lymphocytes migration could lead to novel immunosuppressants. In this project, we will elucidate the structures and functions of proteins involved in the Rac activation pathway, with emphasis on the huge protein DOCK2 consisting of 1828 amino acids. |
Review | - |
CSML File | MPA2.csml |