PINCH-1 Is an Obligate Partner of Integrin-linked Kinase (ILK) Functioning in Cell Shape Modulation, Motility, and Survival

Fukuda, Tomohiko; Chen, Ka; Shi, Xiaohua; Wu, Chuanyue

doi:10.1074/jbc.m309122200

Cited by 193 publications

(280 citation statements)

References 58 publications

Supporting

Mentioning

242

Contrasting

Unclassified

Order By: Relevance

“…Notably, we have observed that RSU1 is consistently downregulated in prostate cancer 3,24,26 , further suggesting a tumor suppressor role for this gene; however, to date, the mechanism by which RSU1 exerts its effects has not been elucidated. Here our model predicted, and we experimentally confirmed that RSU1 interacts with LIMS1, an adaptor protein involved in integrin signaling at focal adhesions 31 . Furthermore, we found that when RSU1 was expressed alone, it had diffuse cytoplasmic localization, but when it was coexpressed with LIMS1, it had discrete punctate cytoplasmic localization (Fig.…”

Section: A N a Ly S I Ssupporting

confidence: 76%

Probabilistic model of the human protein-protein interaction network

et al. 2005

View full text Add to dashboard Cite

A catalog of all human protein-protein interactions would provide scientists with a framework to study protein deregulation in complex diseases such as cancer. Here we demonstrate that a probabilistic analysis integrating model organism interactome data, protein domain data, genomewide gene expression data and functional annotation data predicts nearly 40,000 protein-protein interactions in humans⎯a result comparable to those obtained with experimental and computational approaches in model organisms. We validated the accuracy of the predictive model on an independent test set of known interactions and also experimentally confirmed two predicted interactions relevant to human cancer, implicating uncharacterized proteins into definitive pathways. We also applied the human interactome network to cancer genomics data and identified several interaction subnetworks activated in cancer. This integrative analysis provides a comprehensive framework for exploring the human protein interaction network.We began by assembling a collection of genomic and proteomic data potentially useful in predicting human protein-protein interactions that included model organism protein-protein interactions 1 , protein domain assignments 2 , gene expression measurements in human tissue samples 3 and biological function annotations 4 ( Table 1). Based on previous reports, we suspected that (i) model organism interactions may suggest interactions among orthologous human proteins 5,6 , (ii) similar gene expression profiles across a panel of human tissue samples may identify interacting protein products 7,8 , (iii) protein domain pairs enriched among known human protein-protein interactions may suggest novel interactions 9 , (iv) shared functional annotations from Gene Ontology 4 may suggest physical interactions, and (v) that combining evidence from independent data sources may strongly predict protein-protein interactions [10][11][12] . To test these hypotheses, we applied a naive Bayes classifier 7 , a method well-suited for integrating disparate data types.A gold standard positive set (GSP) of 11,678 distinct protein-protein interactions among 5,505 proteins was queried from the Human Protein Reference Database (HPRD) 12 , a resource that contains known protein-protein interactions manually curated from the literature by expert biologists. A gold standard negative set (GSN) of 3,106,928 protein pairs was defined, in which one protein was assigned to the plasma membrane cellular component and the other to the nuclear cellular component by the Gene Ontology Consortium 4 . Although it is known that membrane proteins can occasionally interact with nuclear proteins, we demonstrated that there are far fewer known interactions within GSN than would be expected by chance (Supplementary Methods online). By averaging the number of interactions per protein in the GSP, we estimated the prior odds of interaction among two randomly selected proteins to be 1 in 381. This is likely an underestimate of the true prior odds because all protein-protein intera...

show abstract

Section: A N a Ly S I Ssupporting

confidence: 76%

Probabilistic model of the human protein-protein interaction network

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Consistently, several lines of evidence have implicated PINCH1/2 as suppressors of apoptosis. For example, in vitro inhibition of PINCH1 expression in HeLa cervical, fibrosarcoma, breast, prostate, hepatocellular, lung, and colon carcinomas leads to apoptosis 109,112 . In vivo, knockout of PINCH1 in embryonic neural crest cells caused enhanced apoptosis 113 .…”

Section: The Ipp Complex (Ilk/pinch and Parvin) And Cancer Biologymentioning

confidence: 99%

Integrin signalling adaptors: not only figurants in the cancer story

et al. 2010

View full text Add to dashboard Cite

Current evidence highlights the ability of adaptor (or scaffold) proteins to create signalling platforms that drive cellular transformation upon integrin-dependent adhesion and growth factor receptor activation. The understanding of the biological effects regulated by these adaptors in tumours might be crucial for the identification of novel targets and the development of innovative therapeutic strategies for human cancer. In this review we will discuss the relevance of adaptor proteins in signalling originating from integrin-mediated cell-extracellular matrix (ECM) adhesion and growth factor stimulation within the context of cell transformation and tumour progression.Herein, we will specifically underline the contribution of p130CAS, NEDD9, CRK, and the IPP complex (ILK, PINCH and PARVIN) to cancer, along with the more recently identified p140CAP.

show abstract

“…In cell culture, reductions in both ILK and PINCH protein levels are observed when either ILK or PINCH levels are depleted either by RNA interference or targeted gene disruption (Fukuda et al, 2003;Xu et al, 2005;Stanchi et al, 2009). A recent publication has also demonstrated mutual stabilization of PINCH and ILK in vivo using antisense morpholinos in zebrafish (Meder et al, 2011).…”

Section: Ilk-pinch-rsu-1 Adhesion Complexes 3187mentioning

confidence: 99%

“…First, the N-terminal LIM domain of PINCH interacts directly with the Nterminal ankyrin repeat domain (ANKR) of ILK Tu et al, 1999). Second, depletion of either ILK or PINCH results in reduction in the levels of the other, indicating a mutual stabilization of these two proteins (Fukuda et al, 2003;Stanchi et al, 2009;Meder et al, 2011). Third, targeted disruption of the interaction between PINCH and ILK in mammalian cell culture experiments by a point mutation in LIM1 of PINCH results in disturbances in cell spreading and survival, as well as reduced stability of both PINCH and ILK (Velyvis et al, 2001;Zhang et al, 2002;Xu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Elias

Pronovost

Cahill

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

Summary PINCH, integrin-linked kinase (ILK) and Ras suppressor-1 (RSU-1) are molecular scaffolding proteins that form a physical complex downstream of integrins, and have overlapping roles in cellular adhesion. In Drosophila, PINCH and ILK colocalize in cells and have indistinguishable functions in maintaining wing adhesion and integrin to actin linkage in the muscle. We sought to determine whether the direct physical interaction between PINCH and ILK was essential for their functions using transgenic flies expressing a version of PINCH with a point mutation that disrupts ILK binding (PINCH Q38A ). We demonstrate that the PINCH-ILK interaction is not required for viability, for integrin-mediated adhesion of the wing or muscle, or for maintaining appropriate localization or levels of either PINCH or ILK. These results suggest alternative modes for PINCH localization, stabilization and linkage to the actin cytoskeleton that are independent of a direct interaction with ILK. Furthermore, we identified a synthetic lethality in flies carrying both the PINCH Q38A mutation and a null mutation in the gene encoding RSU-1. This lethality does not result from PINCH mislocalization or destabilization, and illustrates a novel compensatory role for RSU-1 in maintaining viability in flies with compromised PINCH-ILK binding. Taken together, this work highlights the existence of redundant mechanisms in adhesion complex assembly that support integrin function in vivo.

show abstract

PINCH-1 Is an Obligate Partner of Integrin-linked Kinase (ILK) Functioning in Cell Shape Modulation, Motility, and Survival

Cited by 193 publications

References 58 publications

Probabilistic model of the human protein-protein interaction network

Probabilistic model of the human protein-protein interaction network

Integrin signalling adaptors: not only figurants in the cancer story

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Contact Info

Product

Resources

About