Abstract:
:The normal proto-oncogene c-fms encodes the macrophage growth factor (M-CSF) receptor involved in growth, survival, and differentiation along the monocyte-macrophage lineage of hematopoietic cell development. A major portion of our research concerns unraveling the temporal, molecular, and structural features that determine and regulate these events. Previous results indicated that c-fms can transmit a growth signal as well as a signal for differentiation in the appropriate cells. To investigate the role of the Fms tyrosine autophosphorylation sites in proliferation vs. differentiation signaling, four of these sites were disrupted and the mutant receptors expressed in a clone derived from the myeloid FDC-P1 cell line. These analyses revealed that: (1) none of the four autophosphorylation sites studied (Y697, Y706, Y721, and Y807) are essential for M-CSF-dependent proliferation of the FDC-P1 clone; (2) Y697, Y706, and Y721 sites, located in the kinase insert region of Fms, are not necessary for differentiation but their presence augments this process; and (3) the Y807 site is essential for the Fms differentiation signal: its mutation totally abrogates the differentiation of the FDC-P1 clone and conversely increases the rate of M-CSF-dependent proliferation. This suggests that the Y807 site may control a switch between growth and differentiation. The assignment of Y807 as a critical site for the reciprocal regulation of growth and differentiation may provide a paradigm for Fms involvement in leukemogenesis, and we are currently investigating the downstream signals transmitted by the tyrosine-phosphorylated 807 site. In Fms-expressing FDC-P1 cells, M-CSF stimulation results in the rapid (30 sec) tyrosine phosphorylation of Fms on the five cytoplasmic tyrosine autophosphorylation sites, and subsequent tyrosine phosphorylation of several host cell proteins occurs within 1-2 min. Complexes are formed between Fms and other signal transduction proteins such as Grb2, Shc, Sos1, and p85. In addition, a new signal transduction protein of 150 kDa is detectable in the FDC-P1 cells. The p150 is phosphorylated on tyrosine, and forms a complex with Shc and Grb2. The interaction with Shc occurs via a protein tyrosine binding (PTB) domain at the N-terminus of Shc. The p150 is not detectable in Fms signaling within fibroblasts, yet the PDGF receptor induces the tyrosine phosphorylation of a similarly sized protein. In hematopoietic cells, this protein is involved in signaling by receptors for GM-CSF, IL-3, KL, MPO, and EPO. We have now cloned a cDNA for this protein and found at least one related family member. The related family member is a Fanconia Anemia gene product, and this suggests potential ways the p150 protein may function in Fms signaling.
journal_name
Mol Reprod Devjournal_title
Molecular reproduction and developmentauthors
Rohrschneider LR,Bourette RP,Lioubin MN,Algate PA,Myles GM,Carlberg Kdoi
10.1002/(SICI)1098-2795(199701)46:1<96::AID-MRD15>subject
Has Abstractpub_date
1997-01-01 00:00:00pages
96-103issue
1eissn
1040-452Xissn
1098-2795pii
10.1002/(SICI)1098-2795(199701)46:1<96::AID-MRD15>journal_volume
46pub_type
杂志文章,评审abstract::The sequence of ionic changes involved in initiation of acrosomal exocytosis in capacitated mouse spermatozoa was investigated. Earlier studies demonstrated that a large influx of Na+ is required for exocytosis, this Na+ apparently being associated with an increase in intracellular pH (pHi) via an Na(+)-H+ exchanger. ...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.1080360313
更新日期:1993-11-01 00:00:00
abstract::Primordial germ cells (PGCs) are useful for producing transgenic chickens and preserving genetic material in avian species. In this study, we investigated the in vitro differentiation potential of chicken PGCs into different cell types. For differentiation into adipocytes, chicken PGCs were cultured for 21 days in ind...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.21224
更新日期:2010-09-01 00:00:00
abstract::We have studied the presence of four sperm glycosidases, alpha-mannosidase, alpha-L- fucosidase and two beta-hexosaminidase isoforms, in 11 species of the genus Drosophila spanning approximately an evolutionary 60 MY period, and in Scaptodrosophila lebanonensis, belonging to the ancestor genus Scaptodrosophila. These ...
journal_title:Molecular reproduction and development
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更新日期:2009-01-01 00:00:00
abstract::Activins, the dimeric polypeptides of inhibin beta-subunits, exhibit paracrine effects on cell proliferation, differentiation, and various other cell functions. The complex biological response to activin appears to involve multiple receptors. In the present study, we examined the isoform mRNA expression of both activi...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.1080380103
更新日期:1994-05-01 00:00:00
abstract::Apoptosis is a well-established cellular mechanism for selective cell deletion during development. However, little is known about the expression of an apoptotic pathway and its role in determining the relative sensitivity of the early, pre-gastrula, avian embryo to stress-induced cell death. We examined the sensitivit...
journal_title:Molecular reproduction and development
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doi:10.1002/(SICI)1098-2795(199810)51:2<130::AID-MRD2>
更新日期:1998-10-01 00:00:00
abstract::Rat epididymal glycoprotein DE associates with the dorsal region of the sperm head during sperm maturation, migrates to the equatorial segment (ES) with the acrosome reaction (AR), and is involved in gamete membrane fusion. In the present study we examined the association of DE with the sperm surface and the relations...
journal_title:Molecular reproduction and development
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doi:10.1002/(SICI)1098-2795(200006)56:2<180::AID-MRD9>
更新日期:2000-06-01 00:00:00
abstract::A novel gene Ggnbp1 was identified during yeast two-hybrid screening of gametogenetin protein 1 (GGN1)-interacting proteins. Ggnbp1 gene was found in mouse, rat, and human genomes but not in sequenced yeast, worms, fly, or fish genomes. Northern blotting analysis revealed that the gene was specifically expressed in th...
journal_title:Molecular reproduction and development
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doi:10.1002/mrd.20214
更新日期:2005-03-01 00:00:00
abstract::The objective of the present study was to determine whether Fyn kinase participated in signaling events during sperm-egg interactions, sperm incorporation, and meiosis II. The functional requirement of Fyn kinase activity in these events was tested through the use of the protein kinase inhibitor SKI-606 (Bosutinib) an...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.21034
更新日期:2009-09-01 00:00:00
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journal_title:Molecular reproduction and development
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更新日期:1992-09-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.20620
更新日期:2007-05-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2795(199602)43:2<135::AID-MRD1>
更新日期:1996-02-01 00:00:00
abstract::In newt testis, spermatocytes never appear during winter, because secondary spermatogonia die by apoptosis just before meiosis. In the current study, we examined the effect of low temperatures on spermatogenesis. Incubation of newts at low temperatures (8, 12, 15 degrees C) induced defects in spermatogenesis in a temp...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.10328
更新日期:2003-09-01 00:00:00
abstract::Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase implicated in diverse cellular processes. Activity of GSK-3 is essential for meiotic chromatin segregation in oocytes, yet expression and/or function of GSK-3 have not been reported in mammalian preimplantation embryos. Objectives...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.20495
更新日期:2007-02-01 00:00:00
abstract::Although placental transfer of maternal calcium (Ca(2+)) is a crucial process for fetal development, the biochemical mechanisms are not completely elucidated. Especially, mechanisms of syncytiotrophoblast Ca(2+) extrusion into fetal circulation remain to be established. In the current study we have investigated the ch...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.10303
更新日期:2003-07-01 00:00:00
abstract::Hoechst 33342 (H342), in combination with ultraviolet (UV) irradiation, is frequently used to aid or confirm the enucleation of porcine oocytes in somatic cell nuclear transfer programs. The exposure of oocytes to H342 and UV irradiation has a deleterious effect on the development of in vitro-fertilized porcine oocyte...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.22071
更新日期:2012-09-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.20672
更新日期:2007-09-01 00:00:00
abstract::Smarca 2 (Brahma) and Smarca 4 (Brahma related gene 1, BRG1) alternatively occupy the catalytic site of SWI/SNF chromatin remodeling complexes. Mammalian embryos undergo a dramatic amount of epigenetic remodeling during cleavage development, which plays key roles in regulating both gene transcription and the developme...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.20710
更新日期:2007-10-01 00:00:00
abstract::Demecolcine-induced enucleation (IE) of mouse oocytes has been shown to improve development to term of cloned mice. In this study, we characterized the kinetics and morphological progression of bovine oocytes subjected to IE, and evaluated their ability to support embryo development to the blastocyst stage after nucle...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.20356
更新日期:2005-10-01 00:00:00
abstract::The plasmid DNA, pAcZ, containing Escherichia coli beta-galactosidase (lacZ) gene under the control of chicken beta-actin gene promoter was injected in a linearized form into the germinal disc of fertilized chick ova at the single-cell stage. The manipulated embryos were cultured by the method of Naito et al. (1990) u...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.1080370207
更新日期:1994-02-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
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更新日期:2005-05-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
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更新日期:2006-12-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/1098-2795(200007)56:3<424::AID-MRD13>3.0.C
更新日期:2000-07-01 00:00:00
abstract::The influence of somatic cells on oocyte penetrability was studied during in vitro maturation. Four experiments were carried out. In the first, pig oocytes were fertilized in vitro immediately after collection (immature oocytes) or after being cultured for 44 hr with cumulus cells connected to the whole wall of the ex...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.1080290107
更新日期:1991-05-01 00:00:00
abstract::Successful pregnancy depends on the precise regulation of extravillous trophoblast cell invasion ability. MicroRNA-210-3p (miR-210), which is increased in the placenta of pre-eclampsia. Furthermore, miR-210 could inhibit trophoblasts invasion and might act as a serum biomarker for pre-eclampsia. Previous studies have ...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
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更新日期:2019-07-01 00:00:00
abstract::Previous studies have shown that in adult male mice, expression of the meg1 gene is restricted to meiotic and early postmeiotic testicular germ cells. We have now analyzed the expression of meg1 during postnatal testicular development and the comparable meiotic stages in the female. The 0.75 kb transcript for meg1 beg...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.1080380104
更新日期:1994-05-01 00:00:00
abstract::The sperm nucleus has a unique chromatin structure where the DNA is highly condensed and associated with specific proteins, the protamines. It is a nondividing cell which is also transcriptionally inactive. After fusion with an oocyte, the sperm nucleus undergoes decondensation and, in the same time, starts replicatio...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2795(200003)55:3<307::AID-MRD9>
更新日期:2000-03-01 00:00:00
abstract::Progress in the understanding of early mammalian embryo development has been severely hampered by scarcity of study materials. To circumvent such a constraint, we have developed a strategy that involves a combination of in silico mining of new genes from expressed sequence tags (EST) databases and rapid determination ...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
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更新日期:2001-07-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
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更新日期:1992-05-01 00:00:00
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journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.1080400108
更新日期:1995-01-01 00:00:00
abstract::Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3',5'-adenosine monophosphate (AMP)-response element (CRE) found in a region of the promoter that is homologous to the human INHA promoter. We previously found that during in vitro cytotrophoblast differentiation, human INHA gene expre...
journal_title:Molecular reproduction and development
pub_type: 杂志文章
doi:10.1002/mrd.22421
更新日期:2014-11-01 00:00:00