DENN domain-containing protein 1B

Definition:

Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells. Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Plays a role in clathrin-mediated endocytosis. Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity. Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells.

References:

[1]. Chiao-Wen Yang, et al. Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease. Cell. 2016 Jan 14;164(1-2):141-155. [Content Brief]

[2]. Shin-ichiro Yoshimura, et al. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. J Cell Biol. 2010 Oct 18;191(2):367-81. [Content Brief]

[3]. Andrea L Marat, et al. The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery. J Biol Chem. 2010 Apr 2;285(14):10627-37. [Content Brief]

[4]. Lars Langemeyer, et al. Diversity and plasticity in Rab GTPase nucleotide release mechanism has consequences for Rab activation and inactivation. Elife. 2014 Feb 11;3:e01623. [Content Brief]

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