RAB13 GEFs exchange GTP for GDP on RAB13

Stable Identifier
R-HSA-8876615
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

RAB13 is involved in the trafficking of proteins in the biosynthetic and endosomal recycling pathways and contributes to processes such as tight junction formation and cell adhesion, GLUT 4 transport, angiogenesis, reorganization of the actin cytoskeleton, cell migration and cellular proliferation (Marzesco et al, 2002; Kohler et al, 2004; Morimoto et al, 2005; Terai et al, 2006; Yamamura et al, 2008; Nokes et al, 2008; Sun et al, 2010; Sakane et al, 2010; Sun et al, 2012; Nishikimi et al, 2014; Sun et al, 2016). These processes are often misregulated in cancer cells, and consistent with this, RAB13 has been implicated as a driver of cancer progression and is upregulated in multiple cancer types (Mahadevan et al, 2005; Li et al, 2014; Ioannou et al, 2015; reviewed in Iaonnou and McPherson, 2016). RAB13 is activated at the plasma membrane by its GEFs, DENND1C and DENND2B (also known as ST5), and may also be activated at other sites at lower levels (Yoshimura et al, 2010; Marat et al, 2012; Nishikimi et al, 2014; Ioannou et al, 2015; reviewed in Ishida et al, 2016). In this reaction, GDI and CHM proteins are depicted keeping the inactive, GDP-bound RAB13 soluble, in accordance with the classic view of the RAB cycle. A recent paper, however, provides evidence that in the case of RAB13, inactive RAB13:GDP traffics on vesicles, tethered by interaction with vesicle-bound proteins, and resists GDI-dependent extraction from membranes (Ioannou et al, 2016).

Literature References
PubMed ID Title Journal Year
25713415 DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior J. Cell Biol. 2015
20008558 Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2 Mol. Cell. Biol. 2010
20937701 Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors J. Cell Biol. 2010
18779367 Rab13 regulates membrane trafficking between TGN and recycling endosomes in polarized epithelial cells J. Cell Biol. 2008
22072793 Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton Mol. Biol. Cell 2012
21041651 Rab8A and Rab13 are activated by insulin and regulate GLUT4 translocation in muscle cells Proc Natl Acad Sci U S A 2010
18094055 The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions Mol. Biol. Cell 2008
16525024 JRAB/MICAL-L2 is a junctional Rab13-binding protein mediating the endocytic recycling of occludin Mol. Biol. Cell 2006
27044746 Regulation of Cancer Cell Behavior by the Small GTPase Rab13 J. Biol. Chem. 2016
25074980 Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking Sci Signal 2014
12058051 The small GTPase Rab13 regulates assembly of functional tight junctions in epithelial cells Mol. Biol. Cell 2002
15096524 Rab13 regulates PKA signaling during tight junction assembly J. Cell Biol. 2004
25341920 Rab proteins and the compartmentalization of the endosomal system Cold Spring Harb Perspect Biol 2014
24967941 Bioinformatics analysis reveals disturbance mechanism of MAPK signaling pathway and cell cycle in Glioblastoma multiforme Gene 2014
15528189 Rab13 mediates the continuous endocytic recycling of occludin to the cell surface J. Biol. Chem. 2005
16373702 Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures Mol. Cancer Ther. 2005
27246931 Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases Cell Struct. Funct. 2016
26538022 A complex of Rab13 with MICAL-L2 and ?-actinin-4 is essential for insulin-dependent GLUT4 exocytosis Mol. Biol. Cell 2016
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Participant Of
Catalyst Activity
Catalyst Activity
Title
Rab guanyl-nucleotide exchange factor activity of RAB13 GEFs [cytosol]
Physical Entity
Activity
Orthologous Events