Reactome | Active AKT phosphorylates DENND1A and DENND1B in response to insulin signaling

Active AKT phosphorylates DENND1A and DENND1B in response to insulin signaling

Stable Identifier

R-HSA-8933446

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Active AKT phosphorylates DENND1A and DENND1B in response to insulin signaling

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In response to insulin signaling, active AKT phosphorylates the C-terminal region of RAB35 GEFs DENND1A and DENND1B at at least 2 sites in the C-terminal region. This relieves an autoinhibitory conformation of the GEFs, allowing full GEF activity and promoting RAB35 binding. The open conformation of DENN1D proteins is stabilized subsequent to AKT-mediated phosphorylation by binding of a dimer of the 14-3-3 protein YWHAE. Abrogation of AKT phosphorylation disrupts both 14-3-3 and RAB35 binding to DENND1 proteins (Kulasekaran et al, 2015). Active RAB35 is needed for the insulin-dependent translocation of GLUT4 to the plasma membrane (Davey et al, 2012; Humphrey et al, 2013).

Literature References

PubMed ID	Title	Journal	Year
26055712	Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors Nossova, N, Kulasekaran, G, Lund, I, Cremer, C, Marat, AL, Ioannou, MS, McPherson, PS	J. Biol. Chem.	2015
22762500	TBC1D13 is a RAB35 specific GAP that plays an important role in GLUT4 trafficking in adipocytes Stöckli, J, James, DE, Davey, JR, Lambright, DG, Mishra, AK, Junutula, JR, Humphrey, SJ	Traffic	2012
23684622	Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2 James, DE, Yang, G, Stöckli, J, Fazakerley, DJ, Yang, P, Yang, JY, Humphrey, SJ	Cell Metab.	2013