Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Centaurin-alpha(1) was originally described as a binding partner for phosphoinositides. In spite of the presence of a putative ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) domain, no ARF-GAP activity has been attributed to centaurin-alpha(1) so far. Thus the function of this protein remains to be determined. In order to better understand its intracellular role, we aimed to identify centaurin-alpha(1) partners. Using affinity chromatography followed by mass spectrometry analysis, we identified several potential centaurin-alpha(1) protein partners. Nucleolin, a nucleolar protein involved in ribosome biosynthesis, was the main centaurin-alpha(1) interacting protein. The interaction between centaurin-alpha(1) and nucleolin was confirmed by Western blot analysis and GST pull down assays. Moreover, we have shown that ectopically expressed centaurin-alpha(1) associates in vivo with endogenous nucleolin in human embryonic kidney 293 cells. In addition, the association between nucleolin and centaurin-alpha(1) was disrupted by RNAse treatment, indicating that RNA integrity was necessary for their binding. This suggested that centaurin-alpha(1) was part of a ribonucleoprotein complex.
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PMID:Centaurin-alpha 1 associates in vitro and in vivo with nucleolin. 1256 90

Centaurin-alpha(1) is a phosphatidylinositol 3,4,5-trisphosphate binding protein as well as a GTPase activating protein (GAP) for the ADP-ribosylation factor (ARF) family of small GTPases. To further understand its cellular function, we screened a rat brain cDNA library using centaurin-alpha(1) as bait to identify centaurin-alpha(1) interacting proteins. The yeast two-hybrid screen identified a novel kinesin motor protein as a centaurin-alpha(1) binding partner. The motor protein, termed KIF13B, encoded by a single approximately 9.5-kb transcript, is widely expressed with high levels observed in brain and kidney. Yeast two-hybrid and GST pull-down assays showed that the interaction between centaurin-alpha(1) and KIF13B is direct and mediated by the GAP domain of centaurin-alpha(1) and the stalk domain of KIF13B. Centaurin-alpha(1) and KIF13B form a complex in vivo and the KIF13B interaction appears to be specific to centaurin-alpha(1) as other members of the ARF GAP family did not show any binding activity. We also show that KIF13B and centaurin-alpha(1) colocalize at the leading edges of the cell periphery whereas a deletion mutant of centaurin-alpha(1) that lacks the KIF13B binding site, failed to colocalize with KIF13B in vivo. Finally, we demonstrate that KIF13B binding suppresses the ARF6 GAP activity of centaurin-alpha(1) in intact cells. Together, our data suggest a mechanism where direct binding between centaurin-alpha(1) and KIF13B could concentrate centaurin-alpha(1) at the leading edges of cells, thus modulating ARF6 function.
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PMID:Centaurin-alpha1 interacts directly with kinesin motor protein KIF13B. 1592 60