Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors

Yarden, Yosef; Escobedo, Jaime A.; Kuang, Wun-Jing; Yang‐Feng, Teresa L.; Daniel, Thomas O.; Tremble, Patrice; Chen, E. Y.; Ando, Michael E.; Harkins, Richard N.; Francke, Uta; Fried, Victor A.; Ullrich, Axel; Williams, L T

doi:10.1038/323226a0

Cited by 1,172 publications

(447 citation statements)

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“…The PDGF ligand consists of a disulfide-linked hetero-or homodimer of two related gene products, PDGF-A and PDGF-B (reviewed in Heldin and Westermark, 1989). Two types of PDGF receptors, a and p, have been identified (Yarden et al, 1986;Matsui et al, 1989). The platelet-derived growth factor a receptor (PDGFar) binds PDGF-AA, PDGF-AB, and PDGF-BB, while the platelet-derived growth factor p receptor (PDGFpr) binds PDGF-BB with high affinity, PDGF-AB with low affinity, and PDGF-AA not at all (reviewed in Heldin and Westermark, 1989 PDGF and its receptors have been implicated in many cellular processes including chemotaxis and mitogenesis of connective tissue cells, wound healing, neoplasia, fibrosis, myeloproliferative disease, atherosclerosis, and embryogenesis (reviewed in Ross et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Expression of the platelet‐derived growth factor β receptor during organogenesis and tissue differentiation in the mouse embryo

Shinbrot

Peters

Williams

1994

Developmental Dynamics

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In this study we used in situ hybridization to localize expression of the plateletderived growth factor p (PDGFP) receptor mRNA during organogenesis in the mouse embryo (E 9 . S 16.5). Expression was first seen in periaortic mesenchyme (E 9.5-10.5). Later (E 12.5-E 16.51, the receptor was expressed in the mesenchymal component of many developing tissues and organs, particularly derivatives of the primitive gut. The expression was exceptionally high in mesenchyme directly supporting an epithelium, typical of many developing organs such as the trachea and intestine. However, as the mesenchyme differentiated into smooth muscle, PDGFp receptor mRNA was no longer detected. The expression of the PDGFp receptor mRNA in mesenchymal components of developing organs, along with its absence in epithelial tissues, indicates that it may play a role in mesenchymal-epithelial interactions during organ development. Somewhat unexpectedly, the PDGFP receptor was highly expressed in the endothelium of small blood vessels and vascular structures such as the hyaloid plexus and choroid plexus. In large blood vessels, PDGFp receptor mRNA was found in the mesenchyme surrounding the endothelium. This suggests that the PDGFp receptor is involved in growth and development of blood vessels. o

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Section: Introductionmentioning

confidence: 99%

Expression of the platelet‐derived growth factor β receptor during organogenesis and tissue differentiation in the mouse embryo

Shinbrot

Peters

Williams

1994

Developmental Dynamics

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“…To accomplish this, could ubiquitin be exerting a cell surface-associated role in the degradation of cell attachments to allow for migration away from the streak? This possibility exists since previous studies have demonstrated the presence of stable ubiquitin-cell surface conjugates (Siegelman et al, 1986;Yardin et al, 1986;Leung et al, 1987). In addition, there may be an interaction between ubiquitin and the cytoskeleton to bring about the changes in cell shape that accompany the invagination process (Solursh and Revel, 1978), as stable ubiquitin-cytoskeleton conjugates have been identified (Ball et al, 1987;Murti et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin‐protein conjugates selectively distribute during early chicken embryogenesis

Wunsch

Haas

1995

Developmental Dynamics

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The major mechanism for proteolysis in eucaryotes involves an ATP-dependent pathway for which the covalent attachment of ubiquitin targets proteins for degradation. The involvement of ubiquitin conjugation in early embryonic vertebrate development was investigated by examining the amounts and localization of ubiquitin conjugates at different stages of development in the chicken using an affinity-purified antibody specific for conjugated ubiquitin. Solid phase immunochemical assays measuring whole embryo pools of free and conjugated ubiquitin demonstrated a progressive increase in conjugate pools to stage 18, followed by a decline to stage 24. In contrast, levels of free polypeptide showed a dramatic increase after stage 5, indicating a change in the dynamics of the two pools during development. Immunohistochemistry revealed that the distribution of ubiquitin adducts between stages 3 and 22 was pronounced in regions undergoing extensive cellular remodeling. Ubiquitin conjugates were detected in the primitive streak where cells ingress during gastrulation. The presence of these degradative intermediates in both neuroectodermal cells of the neural folds and subsequent neural crest cells migrating from the dorsum of the neural tube is consistent with an involvement in key morphogenetic events. The localization of ubiquitin conjugates at other selected tissue interfaces including limb bud ectoderrn/mesoderm, and cardiac atrioventricular myocardium/endothelium suggests an active role for ubiquitin-mediated protein modification in similar developmental interactions. Conjugates were distributed first between somites, then in myotomes with a pattern spatially identical to that of the ubiquitin conjugating enzyme, E214K, the major cognate isozyme for isopeptide ligase (E3)-dependent degradation. The potential involvement of ubiquitin conjugation at sites of epithelialmesenchymal associations was further analyzed in culture using atrioventricular canal (AV) endothelium. Immunoreactivity was abundant in cells immediately prior to and during their transformation into mesenchyme. Collectively, the specific temporal and spatial changes in ubiquitin conjugates during early vertebrate development suggest a regulatory role for this degradative path-0 1995 WILEY-LISS, INC. way in the cellular remodeling accompanying embryonic growth and differentiation.Q 1995 Wiley-Liss, Inc.

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“…Abnormal expression of PDGF and its receptors may also contribute to a number of chronic diseases as well as cancer (Fleming et al, 1992). The PDGF system is complicated in that three PDGF isoforms comprised of homo or heterodimers of A and B chains di erentially interact with a and b PDGF receptors (PDGFRs) encoded by two distinct genes (Claesson-Welsh et al, 1988;Matsui et al, 1989a;Yarden et al, 1986). Moreover, there is accumulating evidence that PDGF activation involves recruitment of receptor dimers (Bishayee et al, 1989;Heidaran et al, 1991;Heldin et al, 1989;Seifert et al, 1989;Ueno et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Oncogenic activation of the αPDGFR defines a domain that negatively regulates receptor dimerization

Uren

Karçaaltıncaba

et al. 1997

Oncogene

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The a platelet derived growth factor receptor (aPDGFR) extracellular Immunoglobulin (Ig) like domains 1 ± 3 contain major determinants for ligand interaction. We now report that a deletion of Ig-like loop 3, but not Iglike loop 1 or 2, of the aPDGFR causes ligandindependent transformation in NIH3T3 cells. Biochemical analyses of aPDGFR mutants lacking Ig-like loop 3 indicate that cellular transformation is mediated by ligand-independent activation of the aPDGFR tyrosine kinase activity as determined by receptor autophosphorylation both in vivo and in vitro. Moreover, crosslinking analysis of aPDGFR mutants expressed ectopically in NIH3T3 cells indicate that deletion within extracellular domain 3 leads to ligand-independent receptor dimerization. All of these ®ndings suggest that the Ig-like loop 3 of the aPDGFR contains the major determinants which inhibit receptor dimerization in the quiescent cells and that the ligand binding induces receptor activation by neutralizing the inhibitory e ect of this domain.

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Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors

Cited by 1,172 publications

References 64 publications

Expression of the platelet‐derived growth factor β receptor during organogenesis and tissue differentiation in the mouse embryo

Expression of the platelet‐derived growth factor β receptor during organogenesis and tissue differentiation in the mouse embryo

Ubiquitin‐protein conjugates selectively distribute during early chicken embryogenesis

Oncogenic activation of the αPDGFR defines a domain that negatively regulates receptor dimerization

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