Discoidin domain receptors: a proteomic portrait

Iwai, Leo Kei; Luczynski, Maciej T.; Huang, Paul H.

doi:10.1007/s00018-014-1616-1

Cited by 28 publications

(26 citation statements)

References 90 publications

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“…The two discoidin domain receptors, DDR1 and DDR2 are receptor tyrosine kinases activated specifically by fibrillar collagens I-III and V, but not by individual α-chains, denatured collagen, de-glycosylated, or degraded collagens [10]. A distinct characteristic of these receptors is their slow and sustained activation upon stimulation.…”

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

“…Binding of the discoidin receptors to triple helical collagen leads to tyrosine autophosphorylation with unique activation kinetics, which is followed by receptor internalization [11,12]. Imbalance or dysregulation of DDR1 has been implicated in the development of diseases such as fibrosis, atherosclerosis, arthritis, and cancer [10]. DDR1-null mice are predisposed to osteoarthritis and temporomandibular joint disorder [13], but are protected from atherosclerosis and smooth muscle mineralization [14].…”

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

“…LAIR-1 was also found to be present during osteoclastogenesis and to inhibit this process [34]. LAIR-1 is activated by triple helical collagen, specifically when it encounters the triplet (GPO) 10 (glycine-proline-hydroxyproline) 10 , also known as "collagen related peptide" [31]. LAIR-1 contains two ITIMs, which upon phosphorylation recruit SHP-1 and SHP-2 phosphatases.…”

Section: Leukocyte Receptor Complex (Lrc)mentioning

confidence: 99%

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Collagen Type I as a Ligand for Receptor-Mediated Signaling

et al. 2017

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Collagens form the fibrous component of the extracellular matrix in all multi-cellular animals. Collagen type I is the most abundant collagen present in skin, tendons, vasculature, as well as the organic portion of the calcified tissue of bone and teeth. This review focuses on numerous receptors for which collagen acts as a ligand, including integrins, discoidin domain receptors DDR1 and 2, OSCAR, GPVI, G6b-B, and LAIR-1 of the leukocyte receptor complex (LRC) and mannose family receptor uPARAP/Endo180. We explore the process of collagen production and self-assembly, as well as its degradation by collagenases and gelatinases in order to predict potential temporal and spatial sites of action of different collagen receptors. While the interactions of the mature collagen matrix with integrins and DDR are well-appreciated, potential signals from immature matrix as well as collagen degradation products are possible but not yet described. The role of multiple collagen receptors in physiological processes and their contribution to pathophysiology of diseases affecting collagen homeostasis require further studies.

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Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Section: Leukocyte Receptor Complex (Lrc)mentioning

confidence: 99%

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Collagen Type I as a Ligand for Receptor-Mediated Signaling

et al. 2017

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“…The unique phosphorylation kinetics of DDRs may be translated into distinctive signaling dynamics. However, the precise sig-naling pathways activated by DDRs remain poorly understood (see these comprehensive reviews for a summary of DDR signaling 21,23,26 ). The function of DDRs in physiological and pathological conditions have not been fully elucidated but the emerging picture suggest a complex role for DDRs, which appear to be dependent of the DDR type and the cell/ tissue context.…”

mentioning

confidence: 99%

Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H‐Ras‐induced epithelial to mesenchymal transition

Koh

Woo

Valiathan

et al. 2014

Intl Journal of Cancer

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The epithelial-to-mesenchymal transition (EMT) process allows carcinoma cells to dissociate from the primary tumor thereby facilitating tumor cell invasion and metastasis. Ras-dependent hyperactive signaling is commonly associated with tumorigenesis, invasion, EMT, and metastasis. However, the downstream effectors by which Ras regulates EMT remain ill defined. In this study, we show that the H-Ras pathway leads to mesenchymal-like phenotypic changes in human breast epithelial cells by controlling the ZEB1/microRNA–200c axis. Moreover, H-Ras suppresses the expression of the discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine kinase, via ZEB1, thus identifying ZEB1 as a novel transcriptional repressor of DDR1. Mutation studies on the putative promoter of the DDR1 gene revealed that bipartite Z- and E-box elements play a key role in transcriptional repression of DDR1 in Hs578T and MDA-MB-231 breast carcinoma cell lines by ZEB1. Furthermore, we found an inverse correlation between ZEB1 and DDR1 expression in various cancer cell lines and in human breast carcinoma tissues. Consistently, overexpression of DDR1 reduced the invasive phenotype of mesenchymal-like triple-negative breast cancer cells in 3D cultures and in vivo. Thus, ZEB1’s role in maintenance of EMT in breast carcinoma cells is mediated in part by its ability to suppress DDR1 expression and consequently contribute to the activation of the invasive phenotype. Taken together, our results unveil a novel H-Ras/ZEB1/DDR1 network that contributes to breast cancer progression in triple-negative breast cancers.

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“…Much of what we know of RTK co-activation biology has focused on a number of well-studied RTK families like EGFR, PDGFR, MET and FGFR. Several RTKs (such as the Eph receptors, Discoidin Domain Receptors and pseudokinases like PTK7) that have been identified in tumour phosphoproteomic screens are poorly characterised and there is a need to build on existing foundations and establish the role of these RTKs within co-activation networks in tumour biology (95–100). The effects of autocrine and paracrine ligands on RTK co-activation are also largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

Exploiting receptor tyrosine kinase co-activation for cancer therapy

Tan

Vyse

Huang

2017

Drug Discovery Today

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Studies over the past decade have shown that Receptor Tyrosine Kinase (RTK) co-activation is prevalent in many cancer types. Compelling data demonstrates that cancers are likely to have evolved RTK co-activation as a generic means for driving tumour growth and providing a buffering system to limit the lethal effects of microenvironmental insults including therapy. In this review, we summarise the general principles of RTK co-activation gleaned from key studies over the last decade. We discuss direct and indirect approaches to exploit RTK co-activation for cancer therapy and describe recent developments in computational approaches to predict kinase co-dependencies by integrating drug screening data and kinase inhibitor selectivity profiles. We offer a perspective on the outstanding questions in the field focusing on the implications of RTK co-activation on tumour heterogeneity and cancer evolution and conclude by surveying emerging computational and experimental approaches that will provide further insights into the biology of RTK co-activation and deliver new developments in effective cancer therapies.

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Discoidin domain receptors: a proteomic portrait

Cited by 28 publications

References 90 publications

Collagen Type I as a Ligand for Receptor-Mediated Signaling

Collagen Type I as a Ligand for Receptor-Mediated Signaling

Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H‐Ras‐induced epithelial to mesenchymal transition

Exploiting receptor tyrosine kinase co-activation for cancer therapy

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