PDGF alpha- and beta-receptors activate unique and common signal transduction pathways.

Eriksson, Anders; Siegbahn, Agneta; Westermark, Bengt; Heldin, Carl‐Henrik; Claesson‐Welsh, Lena

doi:10.1002/j.1460-2075.1992.tb05085.x

Cited by 240 publications

(154 citation statements)

References 57 publications

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“…The peptide antiserum R3, raised against the carboxyterminal tail of PDGF b-receptor, and the antiserum R7, against the PDGF a-receptor, have been described previously (Eriksson et al, 1992;Mori et al, 1993). An anti-PDGF areceptor antibody, 951, as well as antibodies against CrkII, CrkL, C3G or RasGAP were purchased from Santa Cruz Biotechnology Inc (USA).…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

“…While both PDGF a-and b-receptors are able to initiate DNA synthesis (Hosang et al, 1989;Matsui et al, 1989), it has been reported that the breceptor is a more potent mediator of mitogenicity compared to the a-receptor in certain cell types (Heidaran et al, 1993;Inui et al, 1994). Moreover, whereas the b-receptor mediates stimulation of chemotaxis, a-receptor inhibits chemotaxis, at least in certain cell types (Eriksson et al, 1992;Koyama et al, 1992;Siegbahn et al, 1990). The two types of receptors also di er in their ability to mediate intracellular calcium mobilization and protein kinase C activation (Block et al, 1989;Diliberto et al, 1992;Salhany et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…Autophosphorylation of the PDGF b-receptor leads to direct binding of phosphatidylinositol 3'-kinase (PI3K), phospholipase C-g (PLC-g), Src family tyrosine kinases, GTPase-activating protein for Ras (RasGAP), the protein tyrosine phosphatase SHP-2, and the adaptor molecules Grb2 and Shc, and the respective binding sites have been identi®ed (Claesson-Welsh, 1994). Among these signal transduction molecules, at least PI3K, PLC-g and SHP-2 also bind to the areceptor (Baznet et al, 1995;Eriksson et al, 1992;Yu et al, 1991). During an analysis of autophosphorylation sites in the a-receptor involved in stimulatory and inhibitory signals for chemotaxis (Yokote et al, 1966), we noticed that Tyr-762 in the receptor is an autophosphorylation site.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

et al. 1998

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Tyr-762 is an autophosphorylation site in the human platelet-derived growth factor (PDGF) a-receptor. In order to investigate whether phosphorylated Tyr-762 serves as a docking site for downstream signal transduction molecules, a nity puri®cation using an immobilized synthetic peptide containing phosphorylated Tyr-762 and its surrounding amino acid residues was performed. Proteins in HeLa cell lysate of molecular sizes 27, 38 and 40 kDa bound to the phosphorylated, but not to the unphosphorylated peptide. Analyses of partial amino acid sequences of the puri®ed proteins indicated that they were identical to CrkI, CrkII and CrkL respectively. The wild-type PDGF a-receptor, when expressed in porcine aortic endothelial cells, formed complexes with CrkII and CrkL upon ligand stimulation, which was speci®cally inhibited by a synthetic peptide containing phosphorylated Tyr-762. Replacement of Tyr-762 with a phenylalanine residue in the PDGF a-receptor abrogated ligand-induced binding of Crk proteins. Tyrosine phosphorylation of CrkII and CrkL increased by 1.8-and 1.3-fold, respectively, upon ligand stimulation of the wild-type areceptor. In contrast, the Y762F mutant PDGF areceptor failed to induce tyrosine phosphorylation of Crk proteins. CrkII and CrkL constitutively formed complex with the guanine nucleotide exchange factor C3G, in unstimulated as well as PDGF-stimulated cells. Moreover, the activated wild-type PDGF a-receptor but not the Y762F mutant receptor was found in a C3G immunoprecipitate, suggesting that a ternary complex between the activated PDGF a-receptor, Crk and C3G was formed. DNA synthesis stimulated by PDGF-BB as well as PDGF-induced MAP kinase activation was similar in cells expressing wild-type and mutant receptors. Interestingly, the activated PDGF b-receptor was found not to bind Crk proteins. Instead, Tyr-771 of the b-receptor, which is localized at an analogous position to Tyr-762 in the a-receptor, binds RasGAP. RasGAP is not bound to the a-receptor.

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Section: Antibodies and Reagentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

et al. 1998

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“…The cellular significance of this complexity is not yet clear, but a detailed comparison of the functional activities of the a-and /?-receptors revealed similarities as well as differences. Whereas both receptors transduce a mitogenie response, only the p-receptor mediated chemotaxis and actin reorganization in the form of circular membrane ruffles [37]. Moreover, in cells having both a-and B-receptors, activation of the a-receptor inhibited B-receptor induced chemotaxis [38,39].…”

Section: Role Of Pkc-o! In ~E~~fftion Of Pi3gf Receptorsmentioning

confidence: 99%

The expression of PDGF‐α but not PDGF‐β receptors is suppressed in Swiss/3T3 fibroblasts over‐expressing protein kinase C‐α

et al. 1994

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The generation and ~hara~te~~tion of Swissf3T3 cells which stably over-express protein kinase C (PKC)-a were previously described by us. In these cells over-exnression of PKC-a reduced the exnression of enidetmal mowth factor (EGF) receutor molecules i(1990) 3. Biol. Chem. 265, 1329&13296]. Here we show that the expression of PdGF-a receptks, but not PDGF-/J receptors; was specifically decreased in these cells. Not only were the levels of PDGF-a receptor mRNA transcript and protein significantly diminished in the PKC-a. over-producing cells, but their ability to respond to short-and long-term growth factor signals was appropriately compromised. This was reflected in a reduced tyrosine autophosphorylation signal in response to PDGF-AA, as well as in decreased growth rates of PKC-d over-expressing cells when supplied with external PDGF-AA. A similar decrease in PDGF-a receptors was also demonstrated in parental Swissf3T3 cells treated with phorbol esters. Our studies imply that P&X-a is involved in a cellular mechanism suppressing the expression of PDGF-a receptors in Swissl3T3 cells. Hence, activation of PKC-a or alterations in its cellular levels may affect, in turn, the expression of a specific set of cell surface receptors and their responses to external growth factors.

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“…[7][8][9] They are implicated in physiologic and pathologic processes, including cell growth and survival, 10 transformation, 11 migration, 12,13 vascular permeability, stroma modulation and wound healing. 14 PDGF binds selectively to receptor subunits, based on specific epitopes; 15,16 PDGF AA binds the PDGFRa, whereas PDGF AB and BB recognize both the PDGFRa and PDGFRb.…”

Section: Introductionmentioning

confidence: 99%

PDGF BB induces VEGF secretion in ovarian cancer

Matei¹,

Kelich²,

Cao³

et al. 2007

Cancer Biology & Therapy

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PDGF alpha- and beta-receptors activate unique and common signal transduction pathways.

Cited by 240 publications

References 57 publications

Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins

The expression of PDGF‐α but not PDGF‐β receptors is suppressed in Swiss/3T3 fibroblasts over‐expressing protein kinase C‐α

PDGF BB induces VEGF secretion in ovarian cancer

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