Structural insights into the interaction of human S100B and basic fibroblast growth factor (FGF2): Effects on FGFR1 receptor signaling

Gupta, Arun; Chou, Ruey Hwang; Li, Hongchun; Yang, Lee Wei; Yu, Chin

doi:10.1016/j.bbapap.2013.09.012

Cited by 23 publications

(23 citation statements)

References 65 publications

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“…2B ). Assignment of the S100B HSQC spectrum was achieved by transfer of chemical shift values from the Biological Magnetic Resonance Bank data set 18995, and confirmed using a three-dimensional, 15 N-separated NOESY, allowing assignment of approximately 92% of the backbone amides ( 27 ). The peak intensity ratios in the presence and absence of twofold Aβ42 were plotted and are marked as a heat map on the S100B structure ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The neuronal S100B protein is a calcium-tuned suppressor of amyloid-β aggregation

et al. 2018

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Section: Resultsmentioning

confidence: 99%

The neuronal S100B protein is a calcium-tuned suppressor of amyloid-β aggregation

et al. 2018

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“…All the above-described functional interactions may be due to different factors, including the sharing of co-receptors, and receptor interactions, but they might also be due to complex interactions between S100A8/A9 proteins and other molecules, like those occurring between S100A4 and amphiregulin [ 58 ] or S100B and basic fibroblast growth factor [ 59 , 60 ]. These interactions might prevent the canonical RAGE engagement by S100A8/A9 and enhance signaling of other receptors, like those of the interacting molecules, as demonstrated to occur when S100B interacts with βFGF [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1

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Padoan

et al. 2014

Cell Communication and Signaling

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BackgroundIn order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines.ResultsNT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation).ConclusionsThe effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

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“…As S100B is an intracellular protein and FGFR1-mediated signaling pathway is involved in the inflammatory effects in synovial tissues ( 20 ), the roles of S100B and FGFR1 were investigated. FGFR1 mRNA and protein expression levels ( Fig.…”

Section: Resultsmentioning

confidence: 99%

S100B regulates inflammatory response during osteoarthritis via fibroblast growth factor receptor 1 signaling

et al. 2018

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The present study aimed to investigate the role of S100B in the inflammation process during osteoarthritis (OA). OA cartilage samples were collected for S100B expression analysis. S100B expression levels were significantly increased in patients with OA compared with the Controls (1.28±0.66 vs. 0.42±0.31; P=0.01) and were determined to be correlated with TNF-α (r=0.42; P=0.04) and IL-1β (r=0.73; P=0.001) expression levels. Orthopedic casting tape was used to immobilize the right knee at 180° extension of adult female New Zealand white rabbits for 4 weeks to establish an OA model. Cartilage specimens from the medial femoral condyle of these rabbits were used for histological confirmation and immunohistochemical analyses, whereas synovial fluid was used in ELISA assays for tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression levels. Human synovial fibroblasts from the knee synovial tissues of normal patients with traumatic injury were transfected with S100B overexpression and knockdown plasmids and subjected to lipopolysaccharide (LPS) stimulation; subsequently, TNF-α and IL-1β expression levels in conditioned medium were determined by ELISA; S100B overexpression and knockdown significantly increased and decreased the TNF-α and IL-1β expression levels, respectively. Increased TNF-α (573.3±15.4 vs. 102.6±8.7 pg) and IL-1β (378.6±7.2 vs. 170.1±5.8 pg) expression levels were detected in OA model rabbits compared with the Control rabbits. Additionally, S100B, fibroblast growth factor (FGF)-1 and FGF receptor (FGFR)-1 mRNA and protein expression levels were increased in OA model rabbits compared with the Control group. FGFR1 knockdown significantly decreased TNF-α and IL-1β expression levels in LPS-stimulated S100B-overexpressing human synovial fibroblasts. S100B is involved in FGFR1 signaling-mediated inflammatory response during OA, which may be considered as a potential therapeutic target.

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Structural insights into the interaction of human S100B and basic fibroblast growth factor (FGF2): Effects on FGFR1 receptor signaling

Cited by 23 publications

References 65 publications

The neuronal S100B protein is a calcium-tuned suppressor of amyloid-β aggregation

The neuronal S100B protein is a calcium-tuned suppressor of amyloid-β aggregation

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1

S100B regulates inflammatory response during osteoarthritis via fibroblast growth factor receptor 1 signaling

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