DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1.
Although the migratory property of lymphocytes is critical for protective immunity, tissue infiltration of lymphocytes sometimes causes harmful immune responses. DOCK2 plays a critical role in lymphocyte migration by regulating actin cytoskeleton through Rac activation, yet the mechanism by which DOCK2 activates Rac remains unknown. We found that DOCK2 associates with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain. When DOCK2 was expressed in T-hybridoma cells lacking endogenous expression of DOCK2, Rac activation and actin polymerization were induced. However, such responses were not elicited by the DOCK2 mutant lacking the region required for ELMO1 binding. On the other hand, we found that the expression of ELMO1 induces Rac activation in the plasmacytoma cells expressing DOCK2 but not ELMO1. These results indicate that the association of DOCK2 with ELMO1 is critical for DOCK2-mediated Rac activation, thereby suggesting that their association might be a therapeutic target for immunologic disorders caused by lymphocyte infiltration.
Sanui
Terukazu
T
Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Inayoshi
Ayumi
A
Noda
Mayuko
M
Iwata
Eiko
E
Stein
Jens V
JV
Sasazuki
Takehiko
T
Fukui
Yoshinori
Y
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D005822:Genetic Vectors; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D015151:Immunoblotting; D008214:Lymphocytes / Q000166:cytology; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D018909:src Homology Domains
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C402110:DOCK2 protein, human; C465214:ELMO1 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein