Protease-induced immunoregulatory activity of platelet factor 4.

Katz, I R; Thorbecke, G. J.; Bell, M K; Yin, Jun; Clarke, Donald A.; Zucker, Marjorie B.

doi:10.1073/pnas.83.10.3491

Cited by 45 publications

(24 citation statements)

References 26 publications

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“…These organelles also possess platelet factor 4 (PF4), which neutralizes the anticoagulant activity of endothelial cell heparin sulfate, induces the chemotaxis of blood cells, and functions as an immunomodulatory and antiangiogenic substance (2,4,13,17,19,34 5' deletions in pPF4GH were made with the Erase-a-Base system. The plasmid was digested with NdeI, and 5' protruding ends were filled with the Klenow fragment as well as a-thiodeoxynucleotide triphosphates.…”

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confidence: 99%

“…1 l, 1991 6118 RAVID ET AL. g for 5 min, washed with 2 ml of CATCH (17), either subjected to botrocetin treatment (see below) or resuspended in 0.3 ml of H20, and lysed by freezing and thawing twice. Adhering cells were scraped off the culture dishes in the presence of 1 ml of ice-cold CATCH, harvested as outlined above, washed with 2 ml of ice-cold CATCH, and lysed as described above.…”

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confidence: 99%

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Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site.

Ravid¹,

Doi²,

Beeler³

et al. 1991

Mol. Cell. Biol.

123

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We used various segments of the 5' upstream region of the rat platelet factor 4 (PF4) gene coupled to the human growth hormone gene and heterologous promoters to identify domains which are critical for tissue-specific expression. Transient expression experiments with rat bone marrow cells and other cell lines revealed a complex interplay between a core promoter domain from -97 to the transcriptional start site and an enhancer/silencer domain from -448 to -112. The core promoter contains a GATA site at -31 to -28 whose mutation to TATA or AATA decreases tissue specificity and moderately affects expression in megakaryocytes as well as a positively acting subdomain from -97 to -83 whose removal decreases overall transcription without affecting tissue specificity. The enhancer/silencer domain possesses three positively acting subdomains from -380 to -362, -270 to -257, and -137 to -120 as well as a negatively acting subdomain at -184 to -151 which is able to reduce overall transcription but has no effect on tissue specificity. The subdomain from -380 to -362 is most critical in restricting gene expression driven either by the PF4 promoter or by a heterologous promoter to the megakaryocytic lineage. The subdomains from -270 to -257 and -137 to -120 function together with the subdomain from -380 to -362 to somewhat increase tissue specificity. Simultaneous mutation of the GATA site and deletion of either the whole enhancer/silencer domain or the subdomain from -380 to -362 or -137 to -120 reduce transcription in megakaryocytes by 10-to 30-fold. On the basis of the above-described results, we propose that the megakaryocyte-specific enhancer/silencer domain and the GATA site are responsible for high-level expression of the PF4 gene in a lineage-specific manner.

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confidence: 99%

Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site.

Ravid¹,

Doi²,

Beeler³

et al. 1991

Mol. Cell. Biol.

123

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“…PF4, an a-granule protein secreted by human platelets, has several biological functions, including procoagulation, antiheparin, chemotactic, and immunoregulatory activities (9,15,18,20). CTAP-III is a platelet-derived Gly-5 peptide bond (5).…”

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confidence: 99%

“…Structure-activity comparisons suggest that this family of proteins contains the following four separate domains: (i) a hydrophobic leader segment that may function in protein secretion, (ii) the amino-terminal domain of the mature protein whose integrity is necessary for the immunoregulatory properties of PF4 (18) and for the growth-stimulatory properties of CTAP-III (5), (iii) a central core region containing the two disulfide bonds, and (iv) a carboxy-terminal domain containing peptide determinants that are necessary for glycosamino-glycan binding and cellular chemotaxis (9,13,33).…”

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confidence: 99%

Identification and characterization of PF4varl, a human gene variant of platelet factor 4.

et al. 1989

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A synthetic DNA probe designed to detect coding sequences for platelet factor 4 and connective tissueactivating peptide III (two human platelet a-granule proteins) was used to identify several similar sequences in total human DNA. Sequence analysis of a corresponding 3,201-base-pair EcoRI fragment isolated from a human genomic library demonstrated the existence of a variait of platelet factor 4, designated PF4varl. The gene for PF4varl consisted of three exons and two introns. Exon 1 coded for a 34-amino-acid hydrophobic leader sequence that had 70% sequence homology with the leader sequence for PF4 but, in contrast, contained a hydrophilic amino-terminal region with four arginine residues. Exon 2 coded for a 42-amino-acid segment that was 100% identical with the corresponding segment of the mature PF4 sequence containing the amino-terminal and disulfide-bonded core regions. Exon 3 coded for the 28-residue carboxy-terminal region corresponding to a domain specifying heparin-binding and cellular chemotaxis. However, PF4varl had amino acid differences at three positions in the lysine-rich carboxy-terminal end that were all conserved among human, bovine, and rat PF4s. These differences should significantly affect the secondary structure and heparin-binding properties of the protein based on considerations of the bovine PF4 crystal structure. By comparing the PF4varl genomic sequence with the known human cDNA and the rat genomic PF4-coding sequences, we identified potential genetic regulatory regions for PF4varl. Rat PF4 and human PF4varl genes had identical 18-base sequences 5' to the promoter region. The intron positions appeared to correspond approximately to the boundaries of the protein functional domains.

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“…This protein contains significant homology to two a-granule platelet proteins, platelet factor 4 (PF4) and ,8-thromboglobulin (/3TG), which are thought to be important mediators in the inflammatory and wound healing responses of platelets. PF4 has been shown to interact with the .immune system in many ways: it is chemotactic for oinocytes and neutrophils (3); it stimulates histamine release from basophils (4); and it augments antibody production in certain experimentally immunosuppressed mice (5). flG has been shown to modulate connective tissue elements; it is chemotactic for fibroblasts (6); and it inhibits prostaglandin I2 production from endothelial cells (7).…”

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confidence: 99%

Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells.

Luster¹,

Jhanwar²,

Chaganti³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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University of Minnesota, Minneapolis, MN 55455 9ommunicated by Lloyd J. Old, December 30, 1986 'AISTRACT An interferon-inducible cytokine, IP-10, containg homology to a family of proteins having chemotactic t-(platelet factor 4, f3-thromboglobulin) and mitogenic (connective tissue-activating peptide HI) activities has been mapped to chromosome 4 at band q21, a locus associated with an acute monocytic/B-lymphocyte lineage leukemia that exhibits the nonrandom translocation t(4;11)(q21;q23 METHODSChromosomal Localization by in Situ Hybridization. Meiotic and somatic chromosome preparations were prepared and hybridized with an IP-10 gene probe as described (10-12). The probe was a pUC plasmid containing a cDNA insert encoding the IP-10 protein (2), which contains the cap site (A.D.L., unpublished results) and two-thirds of the 3'-untranslated region. Plasmid DNA was labeled to high specific activity by nick-translation with [3H]deoxynucleotide triphosphates as described (10). The hybridized and washed slides were exposed for autoradiography (10) 2868The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Protease-induced immunoregulatory activity of platelet factor 4.

Cited by 45 publications

References 26 publications

Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site.

Transcriptional regulation of the rat platelet factor 4 gene: interaction between an enhancer/silencer domain and the GATA site.

Identification and characterization of PF4varl, a human gene variant of platelet factor 4.

Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells.

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