The Anti-HIV Cytokine Midkine Binds the Cell Surface-expressed Nucleolin as a Low Affinity Receptor

Said, Elias A.; Krust, Bernard; Nisole, Sébastien; Svab, Josette; Briand, Jean Paul; Hovanessian, Ara G.

doi:10.1074/jbc.m201194200

Cited by 127 publications

(173 citation statements)

References 63 publications

(108 reference statements)

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“…npg that both heparan-and chondroitin-sulfate proteoglycans are not implicated in the mechanism of binding of MK under our experimental conditions [4]. Consistent with this, the binding of MK to cells is not affected by FGF-2 that uses heparan-sulfate proteoglycans as low affinity receptors [3].…”

Section: Inhibition Of Hiv Infection By Midkine 178supporting

confidence: 86%

“…Indeed, we found out that all the CHO cell lines express high affinity binding sites. Scatchard analysis of the 125 I-labeled MK binding using high and low concentrations confirmed the presence of low affinity and high affinity binding sites, respectively [4]. The estimated Kd value for MK binding to the high affinity binding site on both CHO K1 and CHO 618 cells is 1.5 nM with an estimated 110,000 sites per cell.…”

Section: Inhibition Of Hiv Infection By Midkine 178mentioning

confidence: 69%

“…The fact that HIV attachment is inhibited by two agents which do not compete, illustrates that virus attachment should be coordinated on one hand by heparan sulfate proteoglycans, and on the other hand by nucleolin. Consistent with the critical role of surface nucleolin in the initial steps of HIV infection, the HB-19 pseudopeptide and several physiological ligands of nucleolin (Midkine, Pleiotrophin, lactoferrin) inhibit HIV infection by blocking HIV particle attachment to CD4+ target cells [2][3][4][5][6].…”

mentioning

confidence: 76%

“…In order to evaluate the potential requirement of heparan-and chondroitin-sulfate proteoglycans in the capacity of MK to bind the cell surface, we used Chinese hamster ovary mutant cell lines that are deficient in the expression of heparan sulfate (CHO 677) or both heparan/ chondroitin-sulfate proteoglycans (CHO 618) [21]. Despite lacking proteoglycan expression, these cell lines expressed the cell-surface nucleolin as revealed by the capacity of the biotin-labeled HB-19 to bind and form a stable complex with it [4]. All binding experiments were carried out at 20°C to prevent MK entry into cells.…”

Section: The Binding Of Mk To Cells Does Not Require Heparanand Chondmentioning

confidence: 99%

“…They might be differentially used by MK for specific biological activities [9]. In contrast to the high affinity receptors, the cell-surface expressed nucleolin is the only known low affinity receptor of MK [4]. Besides MK, surface nucleolin serves as a low affinity receptor for PTN [5] and lactoferrin [6].…”

mentioning

confidence: 99%

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Midkine, a cytokine that inhibits HIV infection by binding to the cell surface expressed nucleolin

Hovanessian

2006

Cell Res

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The growth factor midkine (MK) is a cytokine that inhibits HIV infection in cell cultures in an autocrine and paracrine manner by blocking the attachment of HIV particles to permissive cells. MK mRNA is systematically expressed in adult peripheral blood lymphocytes from healthy donors, while its expression becomes markedly but transiently increased upon in vitro treatment of lymphocytes with IL-2 or IFN-g and activation of T lymphocytes by PHA or through the engagement of the CD28 antigen. The binding of MK to cells occurs specifically at a high and a low affinity binding site. This low affinity-binding site is the cell-surface expressed nucleolin, which is implicated in the mechanism of the initial attachment of HIV particles to cells. Accordingly, the nucleolin-binding HB-19 pseudopeptide has no effect on the MK binding to the high affinity binding site, whereas it prevents the binding of MK to the low affinity binding site, thus suggesting the low affinity receptor of MK is the cell-surface-expressed nucleolin. Confocal immunofluorescence laser microscopy revealed the colocalization of MK and the cell-surface-expressed nucleolin at distinct spots. The use of various deletion constructs of nucleolin then indicates that the extreme C-terminal end of nucleolin, containing repeats of the amino acid motif RGG, as the domain that binds MK. The specific binding of MK to the surface nucleolin is independent of heparan sulfate and chondroitin sulfate proteoglycans. After binding to cells, MK enters cells by an active process in which nucleolin and lipid rafts appear to be implicated. The potent and the distinct anti-HIV action of MK along with its enhanced expression in lymphocytes by various physiological stimuli, point out that MK is a cytokine that could be involved in HIV pathogenesis.

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Section: Inhibition Of Hiv Infection By Midkine 178supporting

confidence: 86%

Section: Inhibition Of Hiv Infection By Midkine 178mentioning

confidence: 69%

mentioning

confidence: 76%

Section: The Binding Of Mk To Cells Does Not Require Heparanand Chondmentioning

confidence: 99%

mentioning

confidence: 99%

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Midkine, a cytokine that inhibits HIV infection by binding to the cell surface expressed nucleolin

Hovanessian

2006

Cell Res

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Peptides as Targeting Elements and Tissue Penetration Devices for Nanoparticles

2012

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The use of nanoparticles in medicine (nanomedicine) has recently become an intensely studied field. Nanoparticles carrying drugs and imaging agents have already reached the clinic, but they are essentially passive delivery vehicles, not what are referred to as “smart” nanoparticles. An important function to add to make nanoparticles smarter is active homing to the target tissue. It makes nanoparticles accumulate in the target tissue at higher concentrations than would be the case without this feature, increasing therapeutic efficacy and reducing side effects. This review discusses the recent developments in the nanoparticle targeting field with emphasis on peptides that home to vascular “zip codes” in target tissues and provide a tissue- and cell-penetrating function.

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Upper GI 01–12

2004

British Journal of Surgery

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Aims: Neo-adjuvant therapy followed by surgery is the mainstay of curative treatment for locally advanced oesophageal cancer. Histological response in the neoadjuvant phase is often associated with better survival. The aim of this study was to compare responses in patients undergoing chemotherapy and surgery (CS) or chemoradiotherapy and surgery (CRS) and examine the impact of response on survival. Methods: Forty-seven patients underwent CS and 50 underwent CRS. Response to neo-adjuvant therapy was measured by tumour regression grade (TRG) where Grades 1-3 indicate complete or high degrees of response and Grades 4-5 indicate little or no response. Survival data was analysed using Kaplan-Meier and Cox regression analysis. Results: Although a significantly smaller proportion of patients had TRG 1-3 following CS compared to CRS (8/47 vs. 35/50, P = 0·001) those who responded did equally well in terms of medium-term survival (CS 81% and 52%, CRS 80% and 62·8% at 1 and 3 years). TRG 1-3 was associated with better survival than TRG 4-5 in both groups (overall TRG 1-3: 81% and 60%, TRG 4-5: 61% and 30% at 1 and 3 years, P = 0·02). Conclusions: Significant tumour regression occurs more frequently after chemoradiotherapy and surgery than chemotherapy and surgery. Tumour regression grade is a strong predictor of outcome after both forms of treatment.Upper GI 02

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The Anti-HIV Cytokine Midkine Binds the Cell Surface-expressed Nucleolin as a Low Affinity Receptor

Cited by 127 publications

References 63 publications

Midkine, a cytokine that inhibits HIV infection by binding to the cell surface expressed nucleolin

Midkine, a cytokine that inhibits HIV infection by binding to the cell surface expressed nucleolin

Peptides as Targeting Elements and Tissue Penetration Devices for Nanoparticles

Upper GI 01–12

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