PDGF A-chain gene is expressed by mammalian neurons during development and in maturity

Yeh, Hsiu-Jeng; Ruit, Kenneth G.; Wang, Ya Xian; Parks, William C.; Snider, William D.; Deuel, Thomas F.

doi:10.1016/0092-8674(91)90222-k

Cited by 330 publications

(161 citation statements)

References 26 publications

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“…These observations suggest that PDGF-AA drives certain events during embryogenesis, and also that there is a shift from an autocrine to a paracrine relationship during the development of the mouse embryo (41). Furthermore, expression of PDGF-AA mRNA in neurons and the ␣PDGFR message in glial cells has been shown to be developmentally regulated (66,67). A series of elegant studies examining the role of PDGF-AA (and thus the ␣PDGFR) in the development of the rat optic nerve indicate that PDGF-AA regulates differentiation of the O2A progenitor cells and acts as a survival factor (2,40,44,45).…”

mentioning

confidence: 86%

Phosphorylation of Tyrosine 720 in the Platelet-Derived Growth Factor α Receptor Is Required for Binding of Grb2 and SHP-2 but Not for Activation of Ras or Cell Proliferation

Bazenet

Gelderloos

Kazlauskas

1996

Molecular and Cellular Biology

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Following binding of platelet-derived growth factor (PDGF), the PDGF ␣ receptor (␣PDGFR) becomes tyrosine phosphorylated and associates with a number of signal transduction molecules, including phospholipase C␥-1 (PLC␥-1), phosphatidylinositol 3-kinase (PI3K), the phosphotyrosine phosphatase SHP-2, Grb2, and Src. Here, we present data identifying a novel phosphorylation site in the kinase insert domain of the ␣PDGFR at tyrosine (Y) 720. We replaced this residue with phenylalanine and expressed the mutated receptor (F720) in Patch fibroblasts that do not express the ␣PDGFR. Characterization of the F720 mutant indicated that binding of two proteins, SHP-2 and Grb2, was severely impaired, whereas PLC␥-1 and PI3K associated to wild-type levels. In addition, mutating Y720 to phenylalanine dramatically reduced PDGF-dependent tyrosine phosphorylation of SHP-2. Since Y720 was required for recruitment of two proteins, we investigated the mechanism by which these two proteins associated with the ␣PDGFR. SHP-2 bound the ␣PDGFR directly, whereas Grb2 associated indirectly, most probably via SHP-2, as Grb2 and SHP-2 coimmunoprecipitated when SHP-2 was tyrosine phosphorylated. We also compared the ability of the wild-type and F720 ␣PDGFRs to mediate a number of downstream events. Preventing the ␣PDGFR from recruiting SHP-2 and Grb2 did not compromise PDGF-AA-induced activation of Ras, initiation of DNA synthesis, or growth of cells in soft agar. We conclude that phosphorylation of the ␣PDGFR at Y720 is required for association of SHP-2 and Grb2 and tyrosine phosphorylation of SHP-2; however, these events are not required for the ␣PDGFR to activate Ras or initiate a proliferative response. In addition, these findings reveal that while SHP-2 binds to both of the receptors, it binds in different locations: to the carboxy terminus of the ␤PDGFR but to the kinase insert of the ␣PDGFR.

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mentioning

confidence: 86%

Phosphorylation of Tyrosine 720 in the Platelet-Derived Growth Factor α Receptor Is Required for Binding of Grb2 and SHP-2 but Not for Activation of Ras or Cell Proliferation

Bazenet

Gelderloos

Kazlauskas

1996

Molecular and Cellular Biology

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“…It is well established that PDGF is produced by macrophages (Martinet et al, 1985); accumulation of such cells could explain the finding. Since neuronal cells are sources of PDGF (Sasahara et al, 1991;Yeh et al, 1991) it is not surprising to find measurable amounts of PDGF in other types of non-neoplastic lesions.…”

Section: Discussionmentioning

confidence: 99%

“…PDGF also influences the growth of brain capillary vessels (Smits et al, 1989), and is a chemotactic and angiogenic agent (Grotendorst et al, 1982;Siegbahn et al, 1990;Risau et al, 1992). PDGF in serum originates from platelet a-granules, and more recently it was realised that neuronal cells of the central nervous system (CNS) constitute another important source of PDGF in vivo (Sasahara et al, 1991;Yeh et al, 1991). Structurally, PDGF is a 30 kDa dimer of two homologous disulphide-bonded polypeptide chains denoted A and B, which are encoded by different genes.…”

mentioning

confidence: 99%

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid

Nistér

Enblad²,

Bäckström³

et al. 1994

Br J Cancer

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Summary The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentrations of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and P-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier.

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“…The actions of CNTF and T3 are mediated clearly by a direct, instructive mechanism. These factors and/or their receptors are known to be present and functional during CNS development (Yeh et al 1991;Orr-Urtreger et al 1992;Davis et al 1993;Ip et al 1993;Ware et al 1995). There are few examples of instructive action of soluble ligands on multipotential stem cells.…”

Section: Discussionmentioning

confidence: 99%

Single factors direct the differentiation of stem cells from the fetal and adult central nervous system.

Johe

Hazel²,

Müller³

et al. 1996

Genes Dev.

1,074

865

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Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by muhipotential CNS stem cells.

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PDGF A-chain gene is expressed by mammalian neurons during development and in maturity

Cited by 330 publications

References 26 publications

Phosphorylation of Tyrosine 720 in the Platelet-Derived Growth Factor α Receptor Is Required for Binding of Grb2 and SHP-2 but Not for Activation of Ras or Cell Proliferation

Phosphorylation of Tyrosine 720 in the Platelet-Derived Growth Factor α Receptor Is Required for Binding of Grb2 and SHP-2 but Not for Activation of Ras or Cell Proliferation

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid

Single factors direct the differentiation of stem cells from the fetal and adult central nervous system.

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