Biomedical subjects

T Kishimoto

Publications and source records attributed to T Kishimoto.

At least 253 records · Page 14Linked to original sources

PubMed1998

Identification of major wheat allergens by means of the Escherichia coli expression system.

Wheat proteins were fractionated into salt-soluble, glutenin-rich, and gliadin-rich fractions. Reactivities of these protein fractions with sera of patients with wheat-associated allergies were examined under various conditions. The relative reactivity of the fractions was generally in the order glutenin-rich > gliadin-rich >> salt-soluble fractions, although their reactivities were variable among patients and among the reaction conditions, indicating that the kind, the number and the epitope of allergens were variable among patients. To identify major allergens, alpha-, gamma- and omega-gliadin, and low-molecular-mass (LMM)- and high-molecular-mass (HMM)-glutenin genes were expressed in Escherichia coli by means of a pET vector. Recombinant gliadins and glutenins were partially purified on the basis of the solubilities of prolamin and glutelin. The partially purified recombinant proteins were reacted with the patients' sera. LMM glutenin containing many Gln-Gln-Gln-Pro-Pro motifs, which was identified to be IgE-binding epitope [Tanabe, S., Arai, S., Yanagihara, Y., Mita, H., Takahashi, K. & Watanabe, M. (1996) Biochem. Biophys. Res. Commun. 219, 290-293], exhibited the highest reactivity. The next highest reactivities were observed on alpha-gliadin and gamma-gliadin, which had not been identified as allergens.

Adult↗

PubMed1998

Activation of gp130 transduces hypertrophic signals via STAT3 in cardiac myocytes.

BACKGROUND: gp130, a signal transducer of the IL-6-related cytokines, is expressed ubiquitously, including in the heart. The activation of gp130 in cardiac myocytes was reported to induce myocardial hypertrophy. The downstream side of gp130 consists of two distinct pathways in cardiac myocytes, one a Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, the other a mitogen-activated protein kinase (MAPK) pathway. In the present study, we examined whether the JAK/STAT pathway, especially the STAT3-mediated pathway, plays a critical role in gp130-dependent myocardial hypertrophy by transfecting wild-type and mutated-type STAT3 cDNA to cardiac myocytes. METHODS AND RESULTS: We constructed three kinds of replication-defective adenovirus vectors carrying wild-type (AD/WT) or mutated-type (AD/DN) STAT3 cDNA or adenovirus vector itself (AD). Cultured murine cardiac myocytes infected with adenovirus were stimulated with leukemia inhibitory factor (LIF), and the expression of c-fos and atrial natriuretic factor (ANF) mRNAs and [3H]leucine incorporation were examined. There were no significant differences in MAPK activity among the three groups. Compared with AD-transfected cardiac myocytes, induction of c-fos and ANF mRNAs and protein synthesis after LIF stimulation were significantly augmented in AD/WT-transfected cells. In contrast, induction of c-fos and ANF mRNA expression and protein synthesis were attenuated after LIF stimulation in cardiac myocytes transfected with AD/DN. CONCLUSIONS: These results suggest that the STAT3-dependent signaling pathway downstream of gp 130 promotes cardiac myocyte hypertrophy under stimulation with LIF.

Adenoviridae↗

PubMed1998

Interleukin 6 plays a key role in the development of antigen-induced arthritis.

To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight generations into C57BL/6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6 +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for both IL-1beta and tumor necrosis factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1beta or tumor necrosis factor alpha. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.

Animals↗

PubMed1998

Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice.

The MLL (ALL-1, HRX) gene is frequently involved in chromosomal translocations in acute leukemia and has homology with Drosophila trithorax, which controls homeobox gene expression and embryogenesis. To elucidate the function of Mll, we generated mice with a mutated Mll locus. Mice with a homozygous mutation were embryonic lethal and died at embryonic day 11.5 to 14.5, showing edematous bodies and petechiae. Histological examination revealed that hematopoietic cells were decreased in the liver of homozygous embryos, although they were composed of erythroid, myeloid, monocytic, and megakaryocytic cells with normal differentiation. Colony-forming assays using cells from fetal livers and yolk sacs showed that the number of colonies was markedly reduced and many of the colonies delayed to be recognized in Mllmu/mu embryos, although some of the colonies from Mllmu/mu embryos developed similarly with that from Mll+/+ and Mll+/mu embryos, suggesting the delayed onset of the proliferation of hematopoitic precursors. These data show that the hematopoietic precursors were greatly reduced in mutant mice, and suggest that Mll functions as a regulator of the growth of hematopoietic precursors.

Animals↗

PubMed1998

The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.

Vascularization of organs generally occurs by remodelling of the preexisting vascular system during their differentiation and growth to enable them to perform their specific functions during development. The molecules required by early vascular systems, many of which are receptor tyrosine kinases and their ligands, have been defined by analysis of mutant mice. As most of these mice die during early gestation before many of their organs have developed, the molecules responsible for vascularization during organogenesis have not been identified. The cell-surface receptor CXCR4 is a seven-transmembrane-spanning, G-protein-coupled receptor for the CXC chemokine PBSF/SDF-1 (for pre-B-cell growth-stimulating factor/stromal-cell-derived factor), which is responsible for B-cell lymphopoiesis, bone-marrow myelopoiesis and cardiac ventricular septum formation. CXCR4 also functions as a co-receptor for T-cell-line tropic human immunodeficiency virus HIV-1. Here we report that CXCR4 is expressed in developing vascular endothelial cells, and that mice lacking CXCR4 or PBSF/SDF-1 have defective formation of the large vessels supplying the gastrointestinal tract. In addition, mice lacking CXCR4 die in utero and are defective in vascular development, haematopoiesis and cardiogenesis, like mice lacking PBSF/SDF-1, indicating that CXCR4 is a primary physiological receptor for PBSF/SDF-1. We conclude that PBSF/SDF-1 and CXCR4 define a new signalling system for organ vascularization.

Animals↗

PubMed1998

Bipolar-shape response of human neutrophils to corticotropin-releasing factor.

Human neutrophils in whole blood become bipolar in shape after exposure to chemokinetic stimuli. In normal blood, the proportion of non-spherical neutrophils was 1.2 +/- 0.07% (n = 101). After incubation of blood samples with corticotropin-releasing hormone (CRF, 1 to 20 microM) 36 of 101 subjects exhibited a > or = 10% bipolar-shape ellipsoid response. This ellipsoid response was more frequent in female than in male subjects (32/75 vs. 4/26, p < 0.01). Female Caucasian subjects were more sensitive to CRF than female East Asian subjects (25/48 vs. 2/15, p < 0.01). Age was not a factor in sensitivity to CRF. In young female East Asian subjects (23 +/- 0.4 years, n = 8) that did not manifest the ellipsoid response to CRF, formyl-Met-Leu-Phe (fMLP), a chemotactic peptide, 10(-9) M increased non-spherical neutrophils to 31 +/- 0.8%. In these individuals, the fMLP response was inhibited in a dose-dependent manner by CRF. The pharmacological profile of the stimulatory and fMLP-inhibitory actions of CRF on neutrophil shape was consistent with that of a CRF1-receptor mediated response. Expression of mRNA for the CRF1-receptor was detected in hematopoietic cell lines (e.g., HL-60) using a reverse transcriptase polymerase chain-reaction method. The bipolar-shape response of human neutrophils to CRF has the potential to be a useful indicator of the functional state of this hormone-receptor system in inflammation.

Adult↗

PubMed1998

In vivo regulation of cyclin A/Cdc2 and cyclin B/Cdc2 through meiotic and early cleavage cycles in starfish.

In starfish, fertilization occurs naturally at late meiosis I. In the absence of fertilization, however, oocytes complete meiosis I and II, resulting in mature eggs arrested at the pronucleus stage, which are still fertilizable. In this study, we isolated cDNAs of starfish cyclin A and Cdc2, and monitored extensively the cell cycle dynamics of cyclin A and cyclin B levels and their associated Cdc2 kinase activity, Tyr phosphorylation of Cdc2, and Cdc25 phosphorylation states throughout meiotic and early embryonic cleavage cycles in vivo. In meiosis I, cyclin A was undetectable and cyclin B/Cdc2 alone exhibited histone H1 kinase activity, while thereafter both cyclin A/Cdc2 and cyclin B/Cdc2 kinase activity oscillated along with the cell cycle. Cyclin B-, but not cyclin A-, associated Cdc2 was subjected to regulation via Tyr phosphorylation, and phosphorylation states of Cdc25 correlated with cyclin B/Cdc2 kinase activity with some exceptions. Between meiosis I and II and at the pronucleus stage, cyclin A and B levels remained low, Cdc2 Tyr phosphorylation was undetectable, and Cdc25 remained phosphorylated depending on MAP kinase activity, showing a good correlation between these two stages. Upon fertilization of mature eggs, Cdc2 Tyr phosphorylation reappeared and Cdc25 was dephosphorylated. In the first cleavage cycle, under conditions which prevented Cdc25 activity, cyclin A/Cdc2 was activated with a normal time course and then cyclin B/Cdc2 was activated with a significant delay, resulting in the delayed completion of M-phase. Thus, in contrast to meiosis I, both cyclin A and cyclin B appear to be involved in the embryonic cleavage cycles. We propose that regulation of cyclin A/Cdc2 and cyclin B/Cdc2 is characteristic of meiotic and early cleavage cycles.

Amino Acid Sequence↗

PubMed1998

gp130, the cytokine common signal-transducer of interleukin-6 cytokine family, is downregulated in T cells in vivo by interleukin-6.

gp130 is a common signal-transducing receptor component for the interleukin-6 (IL-6) family of cytokines. To investigate the expression of gp130 in T-cell subsets and its regulation, anti-murine gp130 monoclonal antibody (MoAb) was used for flow cytometric analysis. In normal mice, gp130 was differentially expressed in thymocyte and splenic T-cell subpopulations defined by CD4/CD8 expression. In aged MRL/lpr mice, although gp130 expression was detectable in splenic CD4(+) or CD8(+) T cells, gp130 expression was significantly downregulated. Because serum levels of IL-6 and soluble IL-6 receptor (sIL-6R) are elevated in these mice, we examined the possibility that the downregulation of gp130 expression on splenic T cells might be produced in response to continuous activation of gp130 by high levels of serum IL-6. In transgenic mice overexpressing IL-6, gp130 expression in the splenic T cells was significantly decreased. After stimulation with IL-6 in vitro, the level of gp130 on CD4(+) or CD8(+) splenic T cells from normal mice was significantly decreased. These results suggest that the expression of gp130 in splenic T cells could be downregulated by the IL-6 stimulation under physiological or pathological circumstances.

Aging↗

PubMed1998

TIP49, homologous to the bacterial DNA helicase RuvB, acts as an autoantigen in human.

TATA-binding protein (TBP), a central component for transcriptional regulation, forms complexes with various transcription regulators. We have isolated a novel human cDNA for a 49-kD TBP-interacting protein (TIP49). The human TIP49 was highly homologous to bacterial RuvB proteins that function as a DNA helicase to promote branch migration of the Holliday junction. Immunofluorescence analysis using anti-TIP49 antibody showed a typical dot-shaped nuclear staining pattern, suggesting that TIP49 is included in a macromolecular structure in the nucleus and may participate in nuclear events such as transcription and recombination. Moreover, glycerol gradient analysis demonstrated that TIP49 is present in a macromolecular complex in nuclear extracts. Interestingly, we detected a high level of autoantibodies against TIP49 in sera of patients with autoimmune diseases such as polymyositis/dermatomyositis and autoimmune hepatitis. This indicates that the autoantibody against this protein is a new marker for particular connective tissue diseases. These findings provide further evidence that the macromolecular structures described above are targeted by an autoimmune mechanism. The anti-TIP49 antibodies can be useful probes for clinical diagnosis and for investigation of intranuclear structure.

ATPases Associated with Diverse Cellular Activitie↗

PubMed1998

Identification and characterization of a novel SH3-domain binding protein, Sab, which preferentially associates with Bruton's tyrosine kinase (BtK).

Protein interaction cloning method was used to identify a novel molecule, Sab, which binds to the SH3 domain of Bruton's tyrosine kinase (Btk), the deficient cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia and murine X-linked immunodeficiency. Immunoprecipitation using the anti-Sab antibody identified the protein product of the gene as a 70 kDa molecule. While Sab does not have a proline-rich sequence, it was shown to bind to Btk through the commonly conserved structure among SH3 domains. Remarkably, Sab exhibited a high preference for binding to Btk rather than to other cytoplasmic tyrosine kinases, which suggests a unique role of Sab in the Btk signal transduction pathway.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Activation of phosphatidylinositol 3-kinase through glycoprotein 130 induces protein kinase B and p70 S6 kinase phosphorylation in cardiac myocytes.

Phosphatidylinositol (PI) 3-kinase is known to be activated by cytokine stimulation through different types of receptors to transduce intracellular responses. We have previously reported that leukemia inhibitory factor (LIF) induces the activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein (MAP) kinase pathways through glycoprotein (gp) 130 in cardiac myocytes. However, whether PI 3-kinase is involved in regulation of gp130 signaling and the activation mechanisms by which it associates with other tyrosine-phosphorylated proteins remain unknown. We found that LIF induced the activation of PI 3-kinase in cardiac myocytes. Moreover, JAK1 binds to PI 3-kinase, and LIF stimulation increases the PI 3-kinase activity in JAK1 immunoprecipitates. Activation of MAP kinase and protein kinase B by LIF was attenuated by wortmannin. LIF-induced p70 S6 kinase activation, protein synthesis, and c-fos mRNA expression were inhibited by wortmannin and rapamycin. Both inhibitors failed to appreciably affect the phosphorylation of STAT3. In conclusion, PI 3-kinase is activated with LIF in cardiac myocytes, and JAK1 is found to associate with this enzyme. PI 3-kinase provides a crucial link between gp130, MAP kinase, protein kinase B, and p70 S6 kinase in cardiac myocytes.

Androstadienes↗

PubMed1998

Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells.

The WT1 gene is a tumor-suppressor gene that was isolated as a gene responsible for Wilms' tumor, a childhood kidney neoplasm. We have previously reported that the WT1 gene is strongly expressed in leukemia cells with an increase in its expression levels at relapse and an inverse correlation between its expression levels and prognosis, thus making it a novel tumor marker for leukemic blast cells. Furthermore, WT1 antisense oligomers have been found to inhibit the growth of leukemic cells. These results strongly suggested the involvement of the WT1 gene in human leukemogenesis. The present study was performed to prove our hypothesis that the WT1 gene plays a key role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells, rather than a tumor-suppressor gene function. 32D cl3, an interleukin-3-dependent myeloid progenitor cell line, differentiates into mature neutrophils in response to granulocyte colony-stimulating factor (G-CSF). However, when transfected wild-type WT1 gene was constitutively expressed in 32D cl3, the cells stopped differentiating and continued to proliferate in response to G-CSF. As for signal transduction mediated by G-CSF receptor (G-CSFR), Stat3alpha was constitutively activated in wild-type WT1-infected 32D cl3 in response to G-CSF, whereas, in WT1-uninfected 32D cl3, activation of Stat3alpha was only transient. However, most interesting was the fact that G-CSF stimulation resulted in constitutive activation of Stat3beta only in wild-type WT1-infected 32D cl3, but not in WT1-uninfected 32D cl3. Thus, WT1 expression constitutively activated both Stat3alpha and Stat3beta. A transient activation of Stat1 was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation, but no difference in its activation was found. No activation of MAP kinase was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation. These results demonstrated that WT1 expression competed with the differentiation-inducing signal mediated by G-CSFR and constitutively activated Stat3, resulting in the blocking of differentiation and subsequent proliferation. Therefore, the data presented here support our hypothesis that the WT1 gene plays an essential role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells and represent the first demonstration of an important role of the WT1 gene in signal transduction in hematopoietic progenitor cells.

Animals↗

PubMed1998

The nuclear factor interleukin-6 (NF-IL6) and signal transducer and activator of transcription-3 (STAT-3) signalling pathways co-operate to mediate the activation of the hsp90beta gene by interleukin-6 but have opposite effects on its inducibility by heat shock.

The levels of the 90 kDa heat-shock protein (hsp90) and the activity of the hsp90beta gene promoter are increased in response to treatment by interleukin (IL)-6. The hsp90beta gene promoter contains binding sites for the transcription factors nuclear factor IL-6 (NF-IL6) and signal transducer and activator of transcription 3 (STAT-3), which are activated respectively by the mitogen-activated-protein-kinase and Jak-kinase pathways following IL-6 treatment. Both these factors can activate the hsp90 promoter and have a strong synergistic effect on its activity, which appears to be critical for IL-6-mediated activation of the promoter. Interestingly, the two factors interact differently with the heat-shock factor (HSF) and a heat-shock stress. Thus STAT-3 reduces the stimulatory effect of heat shock whereas NF-IL6 enhances it. When applied together, heat shock and IL-6 produce only weak activation of the hsp90 promoter compared with either stimulus alone, indicating that the inhibitory effect of STAT-3 on HSF predominates under these conditions. In contrast, IL-1, which activates only the NF-IL6 pathway, synergizes with heat shock to produce strong activation of hsp90. These effects are discussed in terms of the multiple stimuli that may regulate the hsp90 promoter in unstressed cells and their interaction with its stress-mediated activation.

CCAAT-Enhancer-Binding Proteins↗

PubMed1998

Interleukin-6 produced by pancreatic carcinoma cells enhances humoral immune responses against tumor cells: a possible event in tumor regression.

Production of interleukin-6 (IL-6) by human pancreatic carcinoma cells inversely correlates with potentials for blood-borne metastasis to the liver in nude mice. IL-6 cDNA was transfected to PCI-43, one of our cultured pancreatic carcinoma cell lines that does not produce IL-6 and generates numerous metastases to the liver. An IL-6 high-producer clone (PCI-43h) generated few metastases; IL-6 production thus has a direct effect on metastasis, whereas other transfectants (PCI-43l and PCI-43n), which are IL-6 low-, and IL-6 non-producers, respectively, did generate metastases. Tumor-reactive IgG, which mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI-43h but not in sera from mice given PCI-43l, PCI-43n or parent PCI-43. Tumor-reactive IgM was detected in sera from all mice, irrespective of inoculated PCI-43 species, with a slight augmentation being noted in PCI-43h-inoculated nude mice. Severe combined immunodeficiency (SCID) beige mice were then used as recipients for PCI-43 species, and tumorigeneity was examined by s.c. inoculation of a suboptimal number of PCI-43 transfectants (1 x 10(6)/0.1 ml). Only PCI-43h formed palpable masses in SCID beige mice, whereas it first grew to be palpable but subsequently became not palpable in nude mice, thereby revealing a dual action of tumor-derived IL-6. Thus, tumor-derived IL-6 confers growth promotion in SCID beige mice, while the same cytokine exhibits anti-tumorigenic functions, presumably through humoral immune responses, in nude mice.

Animals↗

PubMed1998

Deficient expression of Bruton's tyrosine kinase in monocytes from X-linked agammaglobulinemia as evaluated by a flow cytometric analysis and its clinical application to carrier detection.

The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric analysis of intracytoplasmic BTK protein expressed in monocytes was successfully performed. To examine the possible identification of XLA patients and female carriers by this assay, we studied 41 unrelated XLA families with (35) or without (6) known BTK mutations. A flow cytometric assay showed deficient expression of the BTK protein in 40 of 41 patients, complete BTK deficiency in 35, and partial BTK deficiency in 5. One patient exhibited a normal level of BTK expression. All 6 patients with partial BTK deficiency or normal BTK expression had missense BTK mutations. The cellular mosaicism of BTK expression in monocytes from obligate carriers was clearly shown in 35 of 41 families. The results suggested that most BTK mutations in XLA might result in deficient expression of the BTK protein. We conclude that deficient expression of BTK protein can be evaluated by a flow cytometric assay, and the clinical usefulness and limitations in diagnosis of XLA patients and carriers are discussed.

Adolescent↗

PubMed1998

Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis.

OBJECTIVE: To clarify the role of interleukin-6 (IL-6) in the pathogenesis of collagen-induced arthritis (CIA). METHODS: CIA was induced by immunizing twice at a 3-week interval with bovine type II collagen (CII) emulsified with complete adjuvant. Rat anti-mouse IL-6 receptor (anti-IL-6R) monoclonal antibody MR16-1 or isotype-matched control antibody KH-5 was then injected once intraperitoneally. Symptoms of arthritis were evaluated with a visual scoring system, and serum anti-CII antibody and IL-6 levels were measured by enzyme-linked immunosorbent assay. In addition, the CII responsiveness of splenic lymphocytes from mice with CIA was examined. RESULTS: In mice with CIA, excess production of IL-6 in sera was observed within 24 hours after the first CII immunization, and then rapidly decreased. Serum IL-6 increased again beginning 14 days after immunization, in conjunction with the onset of arthritis. When MR16-1 was injected immediately after immunization with CII, it inhibited the development of arthritis in a dose-dependent manner. Furthermore, MR16-1-treated mice exhibited lower serum levels of IgG anti-CII antibody and reduced responsiveness of lymphocytes to CII. This suppressive effect was observed when MR16-1 was injected on day 0 or 3, but not when injected on day 7 or 14. CONCLUSION: IL-6 produced after CII immunization appears to play an essential role in the immunity to CII, and anti-IL-6R antibody reduces the development of CIA by suppressing IL-6 signal transduction.

Animals↗

PubMed1998

Cell cycle arrest and release in starfish oocytes and eggs.

Immature starfish oocytes are arrested at the prophase of meiosis I. Once released from this arrest, meiotic maturation proceeds to the completion of meiosis II in the absence of fertilization, resulting in a second arrest at the female pronucleus stage. This article discusses how Cdc2 kinase is activated in response to the hormone 1-methyladenine at the release from the meiotic prophase arrest, and how MAP kinase is involved in the arrest at the female pronucleus stage. The experimental findings reveal both generality and divergence in the initial Cdc2 kinase activation pathway and in the role of MAP kinase signaling.

Adenine↗

PubMed1998

A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection.

PBSF/SDF-1 is a CXC chemokine which has unique functions among chemokines. It is essential for viability of the embryo, B lymphopoiesis, bone marrow hematopoiesis and cardiogenesis. A receptor for PBSF/SDF-1 was shown to be CXCR4 that is an entry co-receptor for T cell line-tropic HIV-1. Although murine cells had been thought to have no functional co-receptors, murine CXCR4 allowed entry of HIV-1 into target cells with human CD4. In addition, a small molecule CXCR4 inhibitor that blocks HIV-1 entry was identified.

Amino Acid Sequence↗