Interaction of G?? with RACK1 and other WD40 repeat proteins*1

Chen, Songhai; Spiegelberg, Bryan D.; Lin, Fang; Dell, E.J.; Hamm, Heidi E.

doi:10.1016/j.yjmcc.2004.04.019

Cited by 65 publications

(45 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its predicted structure is very similar to the recently published crystal structure of Kluyveromyces lactis Hsv2, a homolog of Atg18 (Baskaran et al, 2012;Krick et al, 2012;Watanabe et al, 2012). WD40 domain-containing proteins often act as scaffolds, which promote and/or coordinate the assembly of protein complexes by creating a stable platform for simultaneous and reversible proteinprotein interactions (Chen et al, 2004;Paoli, 2001;Smith et al, 1999). Atg18 is also able to bind both 5)P 2 ] through a conserved phenylalanine-arginine-arginine-glycine (FRRG) motif within its b-propeller Krick et al, 2006).…”

Section: Introductionsupporting

confidence: 71%

“…There are numerous documented cases, where WD40 domaincontaining proteins associate with their binding partners through amino acid residues present in different parts of the b-propeller (Chen et al, 2004;Cheng et al, 2004;Paoli, 2001;Pashkova et al, 2010). Accordingly, we constructed a number of Atg18 mutants that combine several loop mutants and tested their ability to bind Atg2.…”

Section: Identification Of the Atg2-binding Site Of Atg18mentioning

confidence: 99%

See 1 more Smart Citation

Atg18 function in autophagy is regulated by specific sites within its β-propeller

Rieter

Vinke

Bakula

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryAutophagy is a conserved degradative transport pathway. It is characterized by the formation of double-membrane autophagosomes at the phagophore assembly site (PAS). Atg18 is essential for autophagy but also for vacuole homeostasis and probably endosomal functions. This protein is basically a b-propeller, formed by seven WD40 repeats, that contains a conserved FRRG motif that binds to phosphoinositides and promotes Atg18 recruitment to the PAS, endosomes and vacuoles. However, it is unknown how Atg18 association with these organelles is regulated, as the phosphoinositides bound by this protein are present on the surface of all of them. We have investigated Atg18 recruitment to the PAS and found that Atg18 binds to Atg2 through a specific stretch of amino acids in the b-propeller on the opposite surface to the FRRG motif. As in the absence of the FRRG sequence, the inability of Atg18 to interact with Atg2 impairs its association with the PAS, causing an autophagy block. Our data provide a model whereby the Atg18 b-propeller provides organelle specificity by binding to two determinants on the target membrane.

show abstract

Section: Introductionsupporting

confidence: 71%

Section: Identification Of the Atg2-binding Site Of Atg18mentioning

confidence: 99%

Atg18 function in autophagy is regulated by specific sites within its β-propeller

Rieter

Vinke

Bakula

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…However, despite a wide array of binding partners having been discovered for G␤␥, little is known about This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -04 -0433) on July 2, 2008. how G␤␥ signaling is regulated to ensure precise control of directional cell movement (Hamm, 1998). Recently, we have identified RACK1 as a novel binding partner of G␤␥ (Chen et al, 2004b). RACK1 is a member of the WD40 repeat protein family that is predicted to adopt a ␤-propeller structure similar to that of G␤.…”

Section: Introductionmentioning

confidence: 99%

RACK1 Regulates Directional Cell Migration by Acting on Gβγ at the Interface with Its Effectors PLCβ and PI3Kγ

Chen

Lin

Shin

et al. 2008

MBoC

View full text Add to dashboard Cite

Migration of cells up the chemoattractant gradients is mediated by the binding of chemoattractants to G protein-coupled receptors and activation of a network of coordinated excitatory and inhibitory signals. Although the excitatory process has been well studied, the molecular nature of the inhibitory signals remains largely elusive. Here we report that the receptor for activated C kinase 1 (RACK1), a novel binding protein of heterotrimeric G protein ␤␥ (G␤␥) subunits, acts as a negative regulator of directed cell migration. After chemoattractant-induced polarization of Jurkat and neutrophil-like differentiated HL60 (dHL60) cells, RACK1 interacts with G␤␥ and is recruited to the leading edge. Down-regulation of RACK1 dramatically enhances chemotaxis of cells, whereas overexpression of RACK1 or a fragment of RACK1 that retains G␤␥-binding capacity inhibits cell migration. Further studies reveal that RACK1 does not modulate cell migration through binding to other known interacting proteins such as PKC␤ and Src. Rather, RACK1 selectively inhibits G␤␥-stimulated phosphatidylinositol 3-kinase ␥ (PI3K␥) and phospholipase C (PLC) ␤ activity, due to the competitive binding of RACK1, PI3K␥, and PLC␤ to G␤␥. Taken together, these findings provide a novel mechanism of regulating cell migration, i.e., RACK1-mediated interference with G␤␥-dependent activation of key effectors critical for chemotaxis.

show abstract

“…A common function of WD-40 repeats is to coordinate the assembly of multiprotein complexes (35). Consistent with this, the WD-40 repeat motifs of Lgl has been reported to be involved in binding to target proteins in Drosophila or yeast (36)(37)(38).…”

Section: Discussionmentioning

confidence: 60%

Aberrant Splicing ofHugl-1Is Associated with Hepatocellular Carcinoma Progression

Lü

Feng

Man

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Lethal giant larvae functions as a cell polarity regulator and a tumor suppressor in Drosophila. Its evolutionary conservation implies a tumor suppressor role for its human homologue, Hugl-1. The aims of this study were to characterize Hugl-1 and to determine the clinical significance of Hugl-1 alterations in hepatocellular carcinoma (HCC). Experimental Design: Sequence alterations of Hugl-1 from 80 HCC specimens and 5 HCC cell lines were characterized by reverse transcription-PCR and sequence analysis. Western blot was used for determining Hugl-1 expression. The biological activities of Hugl-1 and its aberrant variants were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound healing assay, Boyden chamber assay, and tumorigenicity assay. Results: In 32.5% (26 of 80) of the specimens and 20.0% (one of five) of HCC cell lines, 23 unique aberrant Hugl-1 transcripts were identified, most of which resulted from skipping part of and/or entire exon or insertion of intron sequences. The majority of these aberrant Hugl-1 transcripts encoded truncated proteins lacking one or more conserved WD-40 repeat motifs. Two truncated Hugl-1 proteins were found exclusively in HCC tissues. Aberrant Hugl-1 transcripts (78.3%, 20 of 23) had a short "direct repeat" sequence flanking their deleted regions. The abnormal Hugl-1 was significantly correlated with poor differentiation and large tumor size of HCC. Overexpression of two representative HCC-derived aberrant Hugl-1 variants promoted HCC cell migration, invasion, and tumorigenicity in nude mice. Conclusions: We provide the first evidence that Hugl-1 mRNA is frequently mutated by aberrant splicing exclusively in HCC, which may be involved in HCC progression.

show abstract

Interaction of G?? with RACK1 and other WD40 repeat proteins*1

Cited by 65 publications

References 87 publications

Atg18 function in autophagy is regulated by specific sites within its β-propeller

Atg18 function in autophagy is regulated by specific sites within its β-propeller

RACK1 Regulates Directional Cell Migration by Acting on Gβγ at the Interface with Its Effectors PLCβ and PI3Kγ

Aberrant Splicing ofHugl-1Is Associated with Hepatocellular Carcinoma Progression

Contact Info

Product

Resources

About