• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Roles of RabGEF1/Rabex-5 domains in regulating Fc epsilon RI surface expression and Fc epsilon RI-dependent responses in mast cells.

RabGEF1/Rabex-5, a guanine nucleotide exchange factor (GEF) for the endocytic pathway regulator, Rab5, contains a Vps9 domain, an A20-like zinc finger (ZnF) domain, and a coiled coil domain. To investigate the importance of these domains in regulating receptor internalization and cell activation, we lentivirally delivered RabGEF1 mutants into RabGEF1-deficient (-/-) mast cells and examined Fc epsilon RI-dependent responses. Wild-type RabGEF1 expression corrected phenotypic abnormalities in -/- mast cells, including decreased basal Fc epsilon RI expression, slowed Fc epsilon RI internalization, elevated IgE + Ag-induced degranulation and IL-6 production, and the decreased ability of -/- cytosol to support endosome fusion. We showed that RabGEF1's ZnF domain has ubiquitin ligase activity. Moreover, the coiled coil domain of RabGEF1 is required for Rabaptin-5 binding and for maintaining basal levels of Rabaptin-5 and surface Fc epsilon RI. However, mutants lacking either of these domains normalized phenotypic abnormalities in IgE + antigen-activated -/- mast cells. By contrast, correction of these -/- phenotypes required a functional Vps9 domain. Thus, Fc epsilon RI-mediated mast cell functional activation is dependent on RabGEF1's GEF activity.

Pubmed ID: 17341663


  • Kalesnikoff J
  • Rios EJ
  • Chen CC
  • Alejandro Barbieri M
  • Tsai M
  • Tam SY
  • Galli SJ



Publication Data

June 15, 2007

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI070813
  • Agency: NIAID NIH HHS, Id: AI23990
  • Agency: NCI NIH HHS, Id: CA72074
  • Agency: NIGMS NIH HHS, Id: GM08205
  • Agency: NHLBI NIH HHS, Id: HL67674

Mesh Terms

  • Bone Marrow Cells
  • Cell Degranulation
  • Cells, Cultured
  • Endocytosis
  • Gene Expression Regulation
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Interleukin-6
  • Mast Cells
  • Receptors, IgE