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Results for “Receptors, CXCR4”

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At least 19 recordsLinked to original sources

PubMed2002

Functional CXCR4 receptor development parallels sensitivity to HIV-1 gp120 in cultured rat astroglial cells but not in cultured rat cortical neurons.

The alpha chemokine receptor CXCR4 is used as the major coreceptor for the cell entry of T-cell-tropic human immunodeficiency virus-1 (HIV-1) isolates. Activation of this coreceptor by its natural ligand SDF1alpha is associated with an intracellular Ca(2+) increase. Because the HIV-1 glycoprotein 120 (gp120) is shedded from the surface of HIV-1-infected cells and is regarded as an injurious molecule in the pathogenesis of HIV-1-associated encephalopathy (HIVE), we investigated the effects of gp120 on the intracellular Ca(2+) regulation of astrocytes and neurons. After 5 days in vitro (DIV), SDF1alpha (50 nM) elicited a pertussis toxin-sensitive intracellular Ca(2+) increase due to Ca(2+) release from internal stores that was reduced by a blocking monoclonal antibody against the CXCR4 receptor in astrocytes and neurons. Parallel with the development of the SDF1alpha response, cells became sensitive to direct application of gp120 (1.25 microg/ml), which, similarly to SDF1alpha, elicited a transient intracellular Ca(2+) increase. However, short-term incubation with gp120 for 60 to 120 min induced a reduction of glutamate- or ATP-evoked intracellular Ca(2+) responses only in astrocytes and not in neurons, although functional CXCR4 receptors were expressed in both cell types. Therefore, our data strongly suggest that the CXCR4 receptor-mediated intracellular signaling pathway of gp120 differs in astrocytes and neurons.

AIDS Dementia Complex↗

PubMed2000

Differential expression of chemokine receptor CXCR4 in Th1 and Th2 subtypes of CD4+ lymphocytes.

Different cytokine profiles allow to divide the CD4+ lymphocytes into Th1, Th2 and Th0 subtypes. It has been observed that the Th2 cells are more efficient supporters for HIV-1 replication than the Th1 cells. The Th1 and the Th2 cells were isolated from peripheral blood lymphocytes of HIV-1 seronegative individuals and the density of CXCR4 receptors was determined by flow cytometry using antibodies directed against the CXCR4 receptor. Flow cytometric analysis revealed higher expression of the HIV-1 co-receptor CXCR4 on Th2 cells than on the Th1, which might explain better replication of HIV-1 viruses in the Th2 cells.

Antibodies↗

PubMed2006

Insight into the binding mode for cyclopentapeptide antagonists of the CXCR4 receptor.

The finding that the chemokine receptor CXCR4 is involved in T-cell HIV entry has encouraged the development of antiretroviral drugs targeting this receptor. Additional evidence that CXCR4 plays a crucial role in both angiogenesis and metastasis provides further motivation for the development of a CXCR4 inhibitor for therapeutic applications in oncology. To facilitate the design of such ligands, we have investigated the possible binding modes for cyclopentapeptide CXCR4 antagonists by docking 11 high/medium affinity cyclopentapeptides to a developed three-dimensional model of the CXCR4 G-protein-coupled receptor's transmembrane region. These ligands, expected to bind in the same mode to the receptor, were docked in the previously deduced receptor-bound conformation [Våbenøet al., in press; doi 10.1002/bip.20508]. Ligand-receptor complexes were generated using an automated docking procedure that allowed ligand flexibility. By comparing the resulting ligand poses, only two binding modes common for all 11 compounds were identified. Inspection of these two ligand-receptor complexes identified several CXCR4 contact residues shown by mutation to be interaction sites for ligands and important for HIV gp120 binding. Thus, the results provide further insight into the mechanism by which these cyclopentapeptides block HIV entry as well as a basis for rational design of CXCR4 mutants to map potential contacts with small peptide ligands.

Amino Acid Sequence↗

PubMed2004

A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow.

Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after transplantation, important for the correction of conditions such as metabolic storage disorders, can occur but with poor efficiency. Substantial improvements in engraftment will be required in order to derive a clinical benefit from MSC transplantation. Chemokines are the most important factors controlling cellular migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in promoting the migration of cells to the bone marrow, via its specific receptor CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its role in mediating migration to bone marrow. We show that CXCR4, although present at the surface of a small subset of MSCs, is important for mediating specific migration of these cells to bone marrow.

Bone Marrow↗

PubMed2005

The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study.

The chemokine receptor CXCR4 is an important factor in the migration, invasiveness, metastasis and proliferation of breast cancer cells. We have retrospectively analyzed the levels of expression of CXCR4 in a large cohort of breast cancers and pre-invasive breast samples linked to clinical data. A total of 1808 invasive breast carcinomas and 214 pre-invasive breast samples could be analyzed in correlation with basic clinico-pathological data such as hormone receptor status, HER2 status and tumor grade. The majority of breast cancers expressed either nuclear or cytoplasmic staining or both. CXCR4 cytoplasmic expression was associated with parameters of tumor aggressivity (tumor grade and lymph node status) and had prognostic value (age-adjusted hazard ratio=1.73; Confidence Interval: 1.07-2.77) with respect to disease-specific survival. CXCR4 positivity in the cytoplasm but not the nucleus was associated with HER2 expression and amplification as well as with hormone receptor negativity (both ER and PR). The percentage of nuclear staining increased from normal breast tissue (20%) to ductal carcinoma-in-situ DCIS (43%) to invasive cancer (67%) while CXCR4 was expressed in the cytoplasm of 67% of (DCIS) cases (double that in normal breast samples), suggesting an important role in breast tumor progression. The CXCR4 receptor is expressed in many breast cancers, justifying its development as a therapeutic target in breast cancer patients. Its cytoplasmic expression is associated with breast tumor progression, suggesting potential value as a diagnostic marker.

Adult↗

PubMed2004

The chemokine receptor CXCR4 and not the N-methyl-D-aspartate receptor mediates gp120 neurotoxicity in cerebellar granule cells.

The human immunodeficiency virus type 1 (HIV-1) glycoprotein gp120 causes neuronal cell death; however, the molecular mechanisms of the neurotoxic effect remain largely unresolved. It has been suggested that gp120 evokes cell death by inducing the release of neurotoxins, including glutamate. The objective of this work was to examine the role of glutamate in gp120-mediated neurotoxicity. We used as an experimental tool cerebellar granule cells prepared from 8-day-old rat cerebella, in which both glutamate and gp120 cause cell death. Cerebellar granule neurons were exposed to gp120 or glutamate alone or in combination with the glutamate receptor antagonist MK801 as well as other antiglutamatergic compounds. Cell viability was measured at various times by using several markers of cell death and apoptosis. MK801, at a concentration that blocked glutamate-induced neuronal cell death, failed to prevent gp120-mediated apoptotic cell death. Moreover, interleukin-10, which has previously been shown to block glutamate toxicity in these neurons, was not neuroprotective against gp120. Because gp120 toxicity is mediated by activation of the chemokine receptor CXCR4, neurons were incubated with the CXCR4 inhibitor AMD3100. This compound prevented gp120- but not glutamate-mediated cell death. These findings suggest that gp120 is toxic to neurons even in the absence of the virus and that the toxic mechanism involves primarily activation of CXCR4 receptor. Therefore, antagonists to the CXCR4 receptor may be more suitable compounds for inhibiting HIV-1 neurotoxicity.

Animals↗

PubMed2003

Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV.

OBJECTIVE: Under some circumstances the HIV virus may infect cells that do not express receptors essential to HIV-entry. We hypothesized that platelet- and megakaryocyte-derived microparticles (MP) could play a role in such infections. MP are circular membrane fragments shed from the surface of eukaryotic cells. After adhesion to target cells, MP may transfer membrane-associated proteins to these cells. We found that peripheral blood platelet- (PMP) and megakaryocyte-derived MP (MegaMP) that highly express CXCR4 may transfer this receptor from the surface of platelets or megakaryocytes to the surface of CXCR4-null cells. DESIGN: Since this mechanism could potentially allow CD4+/CXCR4-null cells to become infected by T-tropic HIV, we incubated several human CD4+/CXCR4-null cells such as normal erythroblasts, glioblastomas U87, MAGI and hematopoietic cell lines UT-7, HEL and TF-1 with PMP or MegaMP. We found that these cells became CXCR4+. We next exposed these cells to X4-HIV (IIIB) and evaluated their susceptibility to infection by PCR, ELISA, and morphological analysis. RESULTS: We observed in all instances that after CD4+/CXCR4-null cell lines 'acquired' CXCR4 from PMP or MegaMP, they could became infected by X4 HIV. CONCLUSIONS: We postulate that both PMP and MegaMP may play a novel and important role in spreading HIV-1 infection by transferring the CXCR4 co-receptor to CD4+/CXCR4-null cells.

Blood Platelets↗

PubMed2006

Characterization of the molecular pharmacology of AMD3100: a specific antagonist of the G-protein coupled chemokine receptor, CXCR4.

The chemokine receptor CXCR4 is widely expressed on different cell types, is involved in leukocyte chemotaxis, and is a co-receptor for HIV. AMD3100 has been shown to be a CXCR4 receptor antagonist, and to block HIV infection of T-tropic, X4-using, virus in vitro and in vivo. AMD3100 is an effective mobilizer of hematopoietic stem cells and is being investigated in clinical trials in multiple myeloma and non-Hodgkins lymphoma patients. Using the CCRF-CEM T-cell line that constitutively expresses CXCR4 we confirmed that AMD3100 was an antagonist of SDF-1/CXCL12 ligand binding (IC50=651+/-37 nM). We have also shown that AMD3100 inhibits SDF-1 mediated GTP-binding (IC50=27+/-2.2 nM), SDF-1 mediated calcium flux (IC50=572+/-190 nM), and SDF-1 stimulated chemotaxis (IC50=51+/-17 nM). AMD3100 did not inhibit calcium flux against cells expressing CXCR3, CCR1, CCR2b, CCR4, CCR5 or CCR7 when stimulated with their cognate ligands, nor did it inhibit receptor binding of LTB4. AMD3100 did not, on its own, induce a calcium flux in the CCRF-CEM cells, which express multiple GPCRs including CXCR4, CCR4 and CCR7. Furthermore, AMD3100 neither stimulated GTP-binding, an assay for GPCR activation, in CEM cell membranes; nor chemotaxis of CCRF-CEM cells. These data therefore demonstrate that AMD3100 is a specific antagonist of CXCR4, is not cross-reactive with other chemokine receptors, and is not an agonist of CXCR4.

Benzylamines↗

PubMed1998

The alpha-chemokine receptor CXCR4 is expressed on the megakaryocytic lineage from progenitor to platelets and modulates migration and adhesion.

CXCR4 is the receptor for the alpha-chemokine stromal cell-derived factor 1 (SDF-1) and has been shown to be expressed on a diversity of leukocytes. In this report, the expression of the CXCR4 receptor in cells of megakaryocytic lineage and the role of SDF-1 in megakaryocytopoiesis were investigated. Using flow cytometry in combination with reverse transcriptase-polymerase chain reaction (RT-PCR), we observed that bone marrow CD34(+), CD61(+) cells, blood platelets, and megakaryocytic leukemia cell lines all expressed the CXCR4 receptor. To examine the expression of the CXCR4 receptor on megakaryocyte progenitors (colony-forming units-megakaryocyte [CFU-Meg]), CXCR4-positive and -negative CD34(+) populations were separated from bone marrow and cultured in a plasma clot culture system. A subpopulation of the CFU-Meg was found in the CXCR4-positive fraction. The functional significance of CXCR4 expression on cells of the megakaryocytic lineage was examined by studying the effects of SDF-1alpha on migration and proliferation of megakaryocyte progenitor cells in vitro. We found that SDF-1alpha potently induced megakaryocyte progenitor migration and significantly enhanced adhesion of mature marrow megakaryocytes to endothelium. No marked effects of SDF-1alpha alone or in combination with thrombopoietin and stem cell factor/kit ligand on megakaryocyte production in vitro were noted. These results demonstrate for the first time that the CXCR4 alpha-chemokine receptor is expressed on cells of the megakaryocytic lineage from progenitors to platelets and that its ligand SDF-1alpha may modulate several aspects of megakaryocytopoiesis.

Antigens, CD34↗

PubMed1997

Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4.

The chemokine receptor CXCR4 is required, together with CD4, for entry by some isolates of HIV-1, particularly those that emerge late in infection. The use of CXCR4 by these viruses likely has profound effects on viral host range and correlates with the evolution of immunodeficiency. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, can inhibit infection by CXCR4-dependent viruses. To understand the mechanism of this inhibition, we used a monoclonal antibody that is specific for CXCR4 to analyze the effects of phorbol esters and SDF-1 on surface expression of CXCR4. On human T cell lines SupT1 and BC7, CXCR4 undergoes slow constitutive internalization (1.0% of the cell surface pool/min). Addition of phorbol esters increased this endocytosis rate >6-fold and reduced cell surface CXCR4 expression by 60 to 90% over 120 min. CXCR4 was internalized through coated pits and coated vesicles and subsequently localized in endosomal compartments from where it could recycle to the cell surface after removal of the phorbol ester. SDF-1 also induced the rapid down modulation (half time approximately 5 min) of CXCR4. Using mink lung epithelial cells expressing CXCR4 and a COOH-terminal deletion mutant of CXCR4, we found that an intact cytoplasmic COOH-terminal domain was required for both PMA and ligand-induced CXCR4 endocytosis. However, experiments using inhibitors of protein kinase C indicated that SDF-1 and phorbol esters trigger down modulation through different cellular mechanisms. SDF-1 inhibited HIV-1 infection of mink cells expressing CD4 and CXCR4. The inhibition of infection was less efficient for CXCR4 lacking the COOH-terminal domain, suggesting at least in part that SDF-1 inhibition of virus infection was mediated through ligand-induced internalization of CXCR4. Significantly, ligand induced internalization of CXCR4 but not CD4, suggesting that CXCR4 and CD4 do not normally physically interact on the cell surface. Together these studies indicate that endocytosis can regulate the cell-surface expression of CXCR4 and that SDF-1-mediated down regulation of cell-surface coreceptor expression contributes to chemokine-mediated inhibition of HIV infection.

Animals↗

PubMed2000

Solubilization of the chemokine receptor CXCR4.

The chemokine receptor CXCR4 was solubilized from the human T-cell line CEM by using the detergent n-dodecyl-beta-maltoside (DDM) and cholesteryl hemisuccinate ester (CHS). Binding studies with (125)I-SDF-1alpha revealed a dissociation constant of 5.33 nM and a receptor density (B(max)) of 2.68 pmol/mg in CEM membranes at 4 degrees C. The affinity of solubilized CXCR4 for SDF-1alpha was identical to membrane-bound CXCR4. Binding of gp120 to solubilized CXCR4 was demonstrated by coprecipitation of gp120 with anti-CXCR4 antibodies.

Cell Line↗

PubMed2002

C-terminal cyclization of an SDF-1 small peptide analogue dramatically increases receptor affinity and activation of the CXCR4 receptor.

In an effort to improve the activities and bioavailabilities of stromal cell-derived factor-1 (SDF-1, CXCL12) sdf-(1-67)-OH (1), we have prepared a linear peptide analogue [sdf-(1-31)-NH(2) (2)] and two lactam analogues [cyclo(Lys(20)-Glu(24))-sdf-(1-31)-NH(2) (3) and cyclo(Glu(24)-Lys(28))-sdf-(1-31)-NH(2) (4)], consisting of the N-terminal region (amino acids 1-14) joined by a four-glycine linker to the C-terminal region (amino acids 56-67) of 1. Analogues 2 and 4 had eight residues of alpha-helix, as estimated from its circular dichroism (CD) spectra, in contrast to 10 residues in analogue 3. Cyclization of analogue 2 at residues 20 and 24 to give analogue 3 resulted in only a slight change to the theta;(222)/theta;(209) ratio (0.81 to 0.86, where 1.09 is considered a perfect alpha-helix), although an increase in the alpha-helix length of analogue 3 was observed. In contrast, cyclization between residues 24 and 28 by lactamization to give analogue 4 only slightly affected the helical content but clearly resulted in a more classical alpha-helical structure (theta;(222)/theta;(209) = 0.98). Cyclization of the linear analogue 2 enhanced the SDF-1 receptor CXCR4 binding approximately 114-fold, where the IC(50) values derived from (125)I-SDF-1 competitive binding assays with CEM cells were found to be 39.5 +/- 5.9 nM, 28.9 +/- 6.3 microM, 225.8 +/- 11.8 nM, and 254.1 +/- 5.4 nM for analogues 1-4, respectively. Intracellular calcium mobilization ([Ca(2+)](i)) induced after interaction with CXCR4, as measured by EC(50), was significantly reduced in analogue 4 compared to 3, and approached the EC(50) of native SDF-1, indicating a correlation between the degree of alpha-helix and biological activity. Therefore, the biological activity of small peptide SDF-1 analogues is highly dependent on the conformation of its C-terminal region.

Amino Acid Sequence↗

PubMedDate not supplied

Antisense phosphorothioate oligonucleotides targeted to the human chemokine receptor CXCR4.

The CXC chemokine receptor CXCR4 is used as a major co-receptor for fusion and entry by syncytia-inducing T-tropic (X4) isolates of HIV-1. In the present study, we report the effects of an antisense oligodeoxyribonucleotide on the inhibition of CXCR4 gene expression in X4 HIV-1 infected HeLa-CD4 cells, to find more efficacious therapeutic possibilities for Human Immunodeficiency Virus type 1 (HIV-1) infection. Antisense phosphorothioate oligodeoxyribonucleotides (anti-S-ODNs) corresponding to the sequence of bases 69 to 88 of the human CXCR4 mRNA gene were synthesized. When the naked anti-S-ODN was incubated with HeLa-CD4 cells, the surface levels of this chemokine receptor were reduced up to 50%, indicating sequence-specific inhibition. We also examined the concomitant use of a basic peptide transfection reagent, nucleosomal histone proteins (RNP), for delivery of anti-S-ODNs. The anti-S-ODN encapsulated with RNP had higher inhibitory effects on p24 products than the naked anti-S-ODN.

Base Sequence↗

PubMed2002

A zebrafish homologue of the chemokine receptor Cxcr4 is a germ-cell guidance receptor.

Germ cells preserve an individual's genetic information and transmit it to the next generation. Early in development germ cells are set aside and undergo a specialized developmental programme, a hallmark of which is the migration from their site of origin to the future gonad. In Drosophila, several factors have been identified that control germ-cell migration to their target tissues; however, the germ-cell chemoattractant or its receptor have remained unknown. Here we apply genetics and in vivo imaging to show that odysseus, a zebrafish homologue of the G-protein-coupled chemokine receptor Cxcr4, is required specifically in germ cells for their chemotaxis. odysseus mutant germ cells are able to activate the migratory programme, but fail to undergo directed migration towards their target tissue, resulting in randomly dispersed germ cells. SDF-1, the presumptive cognate ligand for Cxcr4, shows a similar loss-of-function phenotype and can recruit germ cells to ectopic sites in the embryo, thus identifying a vertebrate ligand-receptor pair guiding migratory germ cells at all stages of migration towards their target.

Animals↗

PubMedDate not supplied

The role of adhesion molecules and chemokine receptor CXCR4 (CD184) in small cell lung cancer.

Small-cell lung cancer (SCLC) is a particularly aggressive form of lung cancer. Responsible for this highly malignant phenotype is an early and widespread metastasis with a high propensity of SCLC cells for bone marrow involvement and the ability to develop resistance against chemotherapeutic agents. Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and adhesion molecules. There is growing evidence that the chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 (CD184) regulate migration and metastasis of a variety of cancers including SCLC. SCLC cells express high levels of functional CXCR4 receptors. Engagement of CXCR4 by CXCL12 leads to an upregulation of integrin-mediated adhesion in SCLC and other tumor cells. Activation of CXCR4 chemokine receptors and integrins on SCLC cells promotes adhesion to accessory cells (such as stromal cells) and extracellular matrix molecules within the tumor microenvironment. These adhesive interactions result in an increased resistance of SCLC cells to chemotherapy. As such, inhibitors of the CXCR4/CXCL12 axis and/or integrin activation may increase the chemosensitivity of SCLC cells and lead to new therapeutic avenues for patients with SCLC.

Carcinoma, Small Cell↗

PubMed2001

High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived factor-1 (SDF-1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF-1 (r = 0.73, P = 0.001). Inhibition of SDF-1-induced migration by an anti-CXCR4 monoclonal antibody (78.33 +/- 23.86% inhibition) evidenced the specificity of CXCR4 to SDF-1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66.12 +/- 66.17) than patients without extramedullary organ infiltration (median 17.56 +/- 19.29; P < 0.001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102.74 +/- 92.13; P < 0.003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.

Antibodies, Monoclonal↗

PubMed2005

Expression of chemokine receptor CXCR4 during chick embryo development.

The chemokine receptor CXCR4 plays a decisive role in physiological cell migration both in developmental processes and adult tissues; it has also been implicated in metastasis formation of different human cancers (Balkwill 2004) and in HIV pathogenesis (Murdoch 2000). Here we present the expression pattern of this important chemokine receptor CXCR4 in the chick embryo. A dynamic expression pattern can be detected beginning as early as the gastrulation stages until the observed stage of HH28. During gastrulation, expression was observed in the epiblast at the level of the primitive streak and in the endoderm. Later, expression was noticeable in the ventral foregut portal, developing somites, tail bud, neural tube, the intermediate mesoderm, Wolffian duct, the lateral plate mesoderm and the developing blood vessels. Our descriptive data suggest a role for CXCR4 in gastrulation and other morphogenetic events connected with angiogenesis and kidney development.

Animals↗

PubMed2003

The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4.

Ubiquitination of the chemokine receptor CXCR4 serves as a targeting signal for lysosomal degradation, but the mechanisms mediating ubiquitination and lysosomal sorting remain poorly understood. Here we report that the Nedd4-like E3 ubiquitin ligase AIP4 mediates ubiquitination of CXCR4 at the plasma membrane, and of the ubiquitin binding protein Hrs on endosomes. CXCR4 activation promotes CXCR4 colocalization with AIP4 and Hrs within the same region of endosomes. Endosomal sorting of CXCR4 is dependent on Hrs as well as the AAA ATPase Vps4, the latter involved in regulating the ubiquitination status of both CXCR4 and Hrs. We propose a model whereby AIP4, Hrs, and Vps4 coordinate a cascade of ubiquitination and deubiquitination events that sort CXCR4 to the degradative pathway.

Adenosine Triphosphatases↗