DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1

Terukazu Sanui, Ayumi Inayoshi, Mayuko Noda, Eiko Iwata, Jens V. Stein, Takehiko Sasazuki, Yoshinori Fukui

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2948-2950
Number of pages3
JournalBlood
Volume102
Issue number8
DOIs
Publication statusPublished - Oct 15 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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