摘要:

AbstractThe high affinity receptors for GM-CSF, IL-3 and IL-5 are heterodimers consisting of a ligand-specific a chain and a commonβchain. These proteins are members of a family of proteins known as the“cytokine receptor family”which is characterized by the presence of a 200-residue ligand-binding module. The GMCSF, IL-3 and IL-5 receptorαchains constitute a distinct subgroup and share features not found in other members of the cytokine receptor family, features which we propose to be important for their interaction with the commonβchain and for their binding of the structurally-related ligands. The growth hormone receptor is a well-characterized member of the cytokine receptor family. Based on the structure of the complex between growth hormone and its receptor, we have proposed sites of contact between the GM-CSF, IL-3 and IL-5 receptors and their cognate ligands.

ISSN:0897-7194    

DOI:10.3109/08977199309046929

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0897-7194    

DOI:10.3109/08977199309046930

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractThe expression of vascular endothelial growth factor (VEGF) in cultured bovine granulosa cells has been studied. As shown by northern blot analysis, granulosa cells express the VEGF gene. Analysis of the VEGF transcripts by the polymerase chain reaction technique shows that granulosa cells express predominantly the smallest VEGF coding forms (VEGF121, and VEGF164). Since in the promoter region of the VEGF gene there are four potential AP-1 sites and two potential AP-2 sites we have studied if TPA and forskolin could regulate VEGF gene expression. TPA induces VEGF transcription in a time- and dose-dependent fashion. Maximal VEGF mRNA levels are detected 6 h after TPA treatment. Induction apparently requires de novo protein synthesis since it does not occur when translation is inhibited by cycloheximide. Forskolin, a naturally occurring diterpene that activates adenylylcyclase, also increases VEGF mRNA content in a time-dependent manner. Induction does not require de novo protein synthesis and, in contrast to TPA, induction is strongly potentiated by cycloheximide. Luteotrophic hormone, a known activator of adenylylcyclase, also induces VEGF transcription. These results imply that granulosa cells may be a source of VEGF which could play a role in the angiogenic process associated with ovulation and corpus luteum formation.

ISSN:0897-7194    

DOI:10.3109/08977199309046931

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractWe have shown previously that (i) retinoic acid (RA), an anti-neoplastic agent, activates the midkine (MK) gene in mammalian embryonic carcinoma cells, and that (ii) the MK of 118 amino acids, purified from L cells, induces neurite outgrowth of mammalian embryonic brain cells. In this paper, we describe an unconventional strategy for the purification of a fully active MK fromE. coliwith a high yield. The MK was overproduced inE. colias a glutathione S-transferase (GST) fusion protein. The MK fusion protein extracted from the bacterial inclusion bodies with guanidine-HCl was renatured, refolded slowly and cleaved by thrombin at the site where the GST links to the MK. The purified free MK, like RA, induced neurite outgrowth from central neurons of the mouse spinal cord, and suppressed the growth of human HL60 leukemia cellsin vitro. Unlike RA, however, the MK did not induce granulocytic differentiation of HL60 cells. Furthermore, the MK supported the survival of an NGF-insensitive sensory neuron subpopulation(s) from chicken embryo dorsal root ganglion. Thus, the actions of the MK and leukemia inhibitory factor (LIF) are surprisingly similar. There is no sequence similarity between MK and LIF, however, and unlike MK, LIF production does not appear to be RA-inducible.

ISSN:0897-7194    

DOI:10.3109/08977199309046932

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractThe response of hemopoietic activity in long term culture of human bone marrow (LTMC) to exogenousc-kitligand has been investigated. Addition ofc-kitligand as recombinant Stem Cell Factor after the adherent stromal cell layer had become confluent failed to increase the content of hemopoietic cells in the culture system. Production of hemopoietic progenitors and differentiated progeny was on the other hand amplified by addition ofc-kitligand at regular intervals from the initiation of the culture, and resulted in net formation of these cells in the culture system. The characteristics of the response were consistent with consequences of increased survival of hemopoietic progenitors during a vulnerable initial phase in which the availability of endogenousc-kitligand was limited by the initially low number of stromal cells. The increase in differentiated progeny was essentially due to increased formation of neutrophil series, and the lack of increased basophil production under these circumstances presumably reflected the nature of the contributory effects of endogenously generated growth regulatory molecules which acted in a synergistic manner with addedc-kitligand.

ISSN:0897-7194    

DOI:10.3109/08977199309046933

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractThe recently identified placenta growth factor gene (PIGF) code for a protein related to the vascular permeability factor (VPF). We present evidence indicating that expression of this gene could be regulated at the post-transcriptional level. The region upstream to the coding region of P1GF mRNA contains a small open reading frame (ORF), potentially coding for a peptide of 15 amino acids. The translation of different constructs in reticulocyte and wheat germ lysates as well as in COS-1 and CV-1 cells indicates that this short region is a translational inhibitory element since mutations in its two potential initiator codons increase PIGF synthesisin vivoUsing RNAse protection assay, we demonstrate that the P1GF mRNAs obtained from human term placenta and JEG choriocarcinoma cell line have a complete 5′untranslated region and, consequently, also the above mentioned small ORF.Finally, the analysis of a bovine P1GF genomic clone reveals that this small ORF is strongly conserved with respect to both putative peptide sequences and distance from the PIGF coding region.

ISSN:0897-7194    

DOI:10.3109/08977199309046934

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractVitamin D3and its analogue calcipotriol (MC 903) inhibit the proliferation of cultured keratinocytes and induce their differentiation. Since TGFβs are very potent inhibitors of keratinocyte growth we studied the effects of vitamin D3and calcipotriol on the secretion of TGFβin cultured murine keratinocytes. Vitamin D, and calcipotriol (10−6- 10−9M) inhibited the DNA-synthesis of mouse keratinocytes by 50–80% in a time and dose-dependent manner as measured by [3H]-thymidine incorporation. Analysis of the conditioned medium of the keratinocytes indicated that the cells secreted into their medium activity that inhibited the growth of indicator Mv1Lu mink lung epithelial cells. Neutralizing antibodies against TGFβ1 and TGFβ2 decreased, and when used together, prevented the observed growth inhibition of the indicator cells. Heat treatment of the conditioned medium, which activates latent forms of TGFβ, revealed higher levels of growth inhibitory activity in the medium from vitamin D3and calcipotriol treated than from control cultures indicating that a fraction of TGFβwas in a latent form. Active TGFβwas, however, detected considerably more in vitamin D3and calcipotriol treated cultures than in control cultures. Immunoblotting analysis of the medium revealed enhanced secretion of TGFβprotein. These results indicate that enhanced TGFβ1 and TGFβ2 secretion and activity is associated with vitamin D3-mediated growth inhibition of cultured keratinocytes.This work was presented in part at the Keystone Symposium“Negative Growth Control”, Keystone, CO, Jan. 26-Feb. 2, 1992 (Koli and Keski-Oja 1992).

ISSN:0897-7194    

DOI:10.3109/08977199309046935

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor