PINCH2 is a new five LIM domain protein, homologous to PINCHand localized to focal adhesions☆

Braun, Attila; Bordoy, Randi; Stanchi, Fabio; Moser, Markus; Kostka, Günter; Ehler, Elisabeth; Brandau, Oliver; Fässler, Reinhard

doi:10.1016/s0014-4827(02)00039-3

Cited by 65 publications

(65 citation statements)

References 45 publications

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“…These observations, together with previous studies, 14 have established that PINCH-1-ILK complex may act as a functional element that plays a crucial role in mediating TGF-␤1-triggered tubular EMT, thereby having significant implications in the pathogenesis of renal interstitial fibrosis. BASIC RESEARCH www.jasn.org PINCH-1 is expressed early in embryonic development and in adult kidney 26 ; however, little is known from the literature about its regulation and function in renal tissues. This study provides clear evidence that PINCH-1 expression at both mRNA and protein levels is induced in the process of tubular EMT triggered by TGF-␤1.…”

Section: Discussionmentioning

confidence: 99%

“…24,26 It primarily localizes at the focal adhesion sites of the culture cells, a pattern that overlaps with other focal adhesion proteins, including ILK. Knockout of PINCH-1 gene in mice and other model organisms such as Caenorhabditis elegans and Drosophila results in developmental defects in cell polarity, cell-matrix adhesion, cell proliferation, and apoptosis, leading to early embryonic death, [27][28][29] phenotypes that resemble the deletion of ILK or ␤1-integrin.…”

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confidence: 99%

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PINCH-1 Promotes Tubular Epithelial-to-Mesenchymal Transition by Interacting with Integrin-Linked Kinase

Dai

et al. 2007

Journal of the American Society of Nephrology

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PINCH-1 is an adaptor protein that binds to the integrin-linked kinase (ILK), an intracellular serine/ threonine protein kinase that plays a critical role in mediating tubular epithelial-to-mesenchymal transition (EMT). To determine whether PINCH-1 is also involved in the EMT process, we investigated its regulation and function during TGF-␤1-stimulated EMT. TGF-␤1 induced PINCH-1 mRNA and protein expression in human proximal tubular epithelial cells in a time-dependent fashion, an effect that was largely dependent on intracellular Smad signaling. Overexpression of PINCH-1 suppressed epithelial markers E-cadherin and ZO-1 and increased fibronectin expression and extracellular assembly, whereas knockdown of PINCH-1 via small interfering RNA reduced TGF-␤1-mediated fibronectin expression and partially restored E-cadherin. PINCH-1 formed a ternary complex with ILK at the focal adhesion sites of tubular epithelial cells. Treatment with an ILK inhibitor or disruption of the ILK/PINCH-1 interaction by overexpressing a dominant-negative N-terminal ankyrin domain of ILK resulted in reduced fibronectin deposition, indicating that the ability of PINCH-1 to stimulate EMT is ILK-dependent. In a mouse model of obstructive nephropathy, PINCH-1 expression increased in a time-dependent manner, suggesting that it may play a role in EMT and renal fibrosis in vivo. We conclude that PINCH-1, through its interaction with ILK, plays an important role in regulating TGF-␤1-mediated EMT and could be a potential future therapeutic target to prevent progression of renal disease.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PINCH-1 Promotes Tubular Epithelial-to-Mesenchymal Transition by Interacting with Integrin-Linked Kinase

Dai

et al. 2007

Journal of the American Society of Nephrology

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“…From the published literature, LIMS1 (Braun et al, 2003) and PPFIBP1 (Serra-Pages et al, 1998) genes were widely expressed in normal human tissues by Northern blot analysis. In contrast, SRPK1 (Papoutsopoulou et al, 1999) and LIAS (Ito et al, 2004) were reported to have restricted tissue expression and to have a cancer-testis-like profile.…”

Section: Isolation Of Cdna Clones Recognised By Igg Antibodies In Thementioning

confidence: 99%

Serological identification of adult T‐cell leukaemia‐associated antigens

et al. 2005

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SummaryAdult T-cell leukaemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Several clinical observations suggest that some tumour-associated antigens in ATL may be recognised by the immune system. In this study, we performed the serological screening of an expression library to identify ATL-associated antigens by using materials from a unique ATL patient with long-term stable disease. Among five distinct genes isolated, serine/arginine protein kinase 1 (SRPK1), which has been reported to have a restricted normal tissue distribution, was found to be overexpressed in most acute type ATL samples, but not in chronic type ATL or in normal peripheral blood mononuclear cells by real-time reverse transcription polymerase chain reaction. Interestingly, the overexpression of SRPK1 in aggressive types of ATL was more exclusively observed at the protein level than at the mRNA level. Autologous antibody to SRPK1 was confirmed in the ATL patient using Western blot analysis with plasma, but not detected in asymptomatic HTLV-I carriers or in healthy volunteers. These results indicate that SRPK1 may be useful for the development of therapeutic and diagnostic methods for patients with ATL.

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“…PINCH-1 interacts with integrin-linked kinase (ILK), another cytoplasmic component of cell-ECM adhesions (13)(14)(15), through the N-terminal-most LIM domain of PINCH-1 and the N-terminal ankyrin (ANK) repeat domain of ILK (11,12,16). The second member of the PINCH family, PINCH-2, has recently been identified (17)(18)(19). PINCH-2, like PINCH-1, interacts with ILK and localizes to cell-ECM adhesions (18).…”

mentioning

confidence: 99%

“…PINCH-2, like PINCH-1, interacts with ILK and localizes to cell-ECM adhesions (18). Both PINCH proteins are widely expressed (18,19) and they are co-expressed in at least certain human cells (18). In addition to interacting with the PINCH proteins through the N-terminal ANK domain, ILK, through its C-terminal domain, interacts with several other focal adhesion proteins including ␤ 1 integrins (13), CH-ILKBP/actopaxin/␣-parvin (abbreviated as ␣-parvin herein) (20 -22), affixin/␤-parvin (22,23), and paxillin (24).…”

mentioning

confidence: 99%

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

Fukuda

Chen

Shi

et al. 2003

Journal of Biological Chemistry

193

242

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PINCH2 is a new five LIM domain protein, homologous to PINCHand localized to focal adhesions☆

Cited by 65 publications

References 45 publications

PINCH-1 Promotes Tubular Epithelial-to-Mesenchymal Transition by Interacting with Integrin-Linked Kinase

PINCH-1 Promotes Tubular Epithelial-to-Mesenchymal Transition by Interacting with Integrin-Linked Kinase

Serological identification of adult T‐cell leukaemia‐associated antigens

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

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