Diverse receptors for fibroblast growth factors

Partanen, Juha; Vainikka, Satu; Korhonen, Jaana; Armstrong, Elina; Alitalo, Kari

doi:10.1016/0955-2235(92)90005-3

Cited by 108 publications

(49 citation statements)

References 60 publications

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“…Thus far, only one Src homology 2 (SH2) domain-containing protein, phospholipase C-␥ (PLC-␥), has been shown to bind directly to FGF receptor-1, via a carboxyl-terminal autophosphorylation site at Tyr-766 in the receptor (25). The FGF receptors are known to mediate a variety of cellular responses, such as cell proliferation, migration, and differentiation (23,24). We have previously shown that murine brain capillary endothelial cells respond to FGF-1 and FGF-2 treatment either by proliferation or by differentiation, the latter visualized in vitro as tube formation of cells cultured in collagen gels (26).…”

Section: P70mentioning

confidence: 99%

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Phosphatidylinositol 3′-Kinase-independent p70 S6 Kinase Activation by Fibroblast Growth Factor Receptor-1 Is Important for Proliferation but Not Differentiation of Endothelial Cells

Kanda

Hodgkin

Woodfield

et al. 1997

Journal of Biological Chemistry

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p70s6k has a role in cell cycle progression in response to specific extracellular stimuli. The signal transduction pathway leading to activation of p70 s6k by fibroblast growth factor receptor-1 (FGFR-1) was examined in FGF-2-treated rat L6 myoblasts. p70 s6k was activated in a biphasic and rapamycin-sensitive manner. Although phosphatidylinositol 3-kinase was not activated in the FGF-2 treated cells, as judged from in vitro and in vivo analyses, wortmannin and LY294002 treatment inhibited p70 s6k activation. Inhibition of protein kinase C (PKC), by bisindolylmaleimide or by chronic phorbol ester treatment of the FGFR-1 cells, suppressed but did not block p70 s6k activation. In cells expressing a pointmutated FGFR-1, Y766F, unable to mediate PKC activation, p70 s6k was still activated, in a bisindolylmaleimideand phorbol ester-resistant manner. The involvement of S6 kinase in FGFR-1-dependent biological responses was examined in murine brain endothelial cells. In response to FGF-2, these cells differentiate to form tubelike structures in collagen gel cultures and proliferate when cultured on fibronectin. p70 s6k was not activated in endothelial cells on collagen, whereas activation was observed during proliferation on fibronectin. In agreement with this finding, rapamycin inhibited the proliferative but not the differentiation response. Our results indicate that FGFR-1 mediates p70 s6k activation by a phosphatidylinositol 3-kinase-independent mechanism that does not require PKC activation and, furthermore, proliferation, but not differentiation of endothelial cells in response to FGF-2, is associated with p70 s6k activation.The p70 S6 kinase (p70 s6k ) 1 is a serine/threonine kinase that phosphorylates 40 S ribosomal protein S6, in response to a number of extracellular stimuli (1, 2). The two isoforms of p70 s6k , the 70-kDa s6k ␣II (cytosolic form) and the 85-kDa s6k ␣I (nuclear form), are derived from alternatively spliced products (3, 4) from a single gene (3). Extracellular stimuli induce acute phosphorylation on multiple serine and threonine residues within p70 s6k , which are associated with its activation. Four of these residues are located in the carboxyl terminus of p70 s6k (5). These sites are potential mitogen-activated protein kinase targets. However, mitogen-activated protein kinase fails to activate p70 s6k after phosphorylation of these sites in vitro (6), and p70 s6k activation lies on a Ras-independent pathway (7,8). Protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3-kinase), and protein kinase B have been implicated as upstream signaling molecules of p70 s6k activation in insulin-, platelet-derived growth factor (PDGF)-, epidermal growth factor (EGF)-and interleukin-2-treated cells (9). Recently, p70 s6k was moreover shown to complex with and to be activated by the GTP-binding Rho family proteins Rac1 and Cdc42 (10). However, the relative contribution of these pathways to activation of p70 S6K is unclear (8). Rapamycin is a potent and specific inhibitor of p70 s6k , preventing phosphory...

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Section: P70mentioning

confidence: 99%

“…Extracellular signaling by FGFs is transduced via specific receptor tyrosine kinases, denoted FGF receptor-1 to -4 (23,24). Heparin and heparan sulfate proteoglycans are known to modulate ligand binding to the receptor tyrosine kinase.…”

Section: P70mentioning

confidence: 99%

Phosphatidylinositol 3′-Kinase-independent p70 S6 Kinase Activation by Fibroblast Growth Factor Receptor-1 Is Important for Proliferation but Not Differentiation of Endothelial Cells

Kanda

Hodgkin

Woodfield

et al. 1997

Journal of Biological Chemistry

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“…So far, receptors encoded by at least four separate genes (FGFR1-4) have been identified (Basilico and Moscatelli, 1992;Givol and Yayon, 1992;Jaye et al, 1992;Partanen et al, 1992). This family of receptors is further complicated by an array of spliced variants that vary in their extraor intracellular domains, resulting in potentially truncated forms (Givol and Yayon, 1992;Jaye et al, 1992;Partanen et al, 1992).The function of most of these receptor isoforms is unknown. We have demonstrated the presence of FGFR1 and FGFR2 mRNA in both normal and breast cancer samples as well as a panel of breast cell lines and normal human tissues (Luqmani et al, 1992a), and Jacquemier et al (1994) have also demonstrated the presence of FGFR1 mRNA in normal and malignant breast epithelial cells using in situ hybridization.…”

mentioning

confidence: 99%

“…The high-affinity receptors for FGF belong to the tyrosine kinase superfamily of receptors. So far, receptors encoded by at least four separate genes (FGFR1-4) have been identified (Basilico and Moscatelli, 1992;Givol and Yayon, 1992;Jaye et al, 1992;Partanen et al, 1992). This family of receptors is further complicated by an array of spliced variants that vary in their extraor intracellular domains, resulting in potentially truncated forms (Givol and Yayon, 1992;Jaye et al, 1992;Partanen et al, 1992).…”

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confidence: 99%

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue

Coope

Browne²,

Yiangou³

et al. 1997

Br J Cancer

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Summary Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly seen in normal epithelial cells. However, polymerase chain reaction (PCR) analysis and immunoblotting of isolated normal epithelial and myoepithelial cells showed FGF1 mRNA and protein to be present in both cell types. Following incubation of frozen sections at 370C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjacent to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. In contrast, FGF1 staining was found to be associated with the stroma adjacent to malignant cells only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was localized to both normal and malignant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptors between normal and cancer samples. The change in location of FGF1 between normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both autocrine and paracrine roles for FGF1 in the normal and malignant human breast.Keywords: breast cancer; fibroblast growth factor 1; protease; immunohistochemistry Fibroblast growth factor 1 (FGF1) belongs to a family of multifunctional polypeptides that are involved in a wide array of biological processes, which include cellular proliferation and differentiation, angiogenesis, chemotaxis, embryonal development and tissue repair (Basilico and Moscatelli, 1992). To date, the FGFs consist of a family of nine homologous polypeptide growth factors that include FGF1 (acidic FGF), FGF2 (basic FGF), FGF3 (int-2), FGF4 (hst-l/Kaposi FGF), FGF5, FGF6 (hst-2), FGF7 (keratinocyte growth factor), FGF8 (androgen-induced growth factor) and FGF9 (glial-activating factor) (Basilico and Moscatelli, 1992;Tanaka et al, 1992;Miyamoto et al, 1993). These proteins share 35-50% overall homology of their amino acid sequences (Basilico and Moscatelli, 1992;Givol and Yayon, 1992).Unlike other members of the family, FGF1, FGF2 and FGF9 are synthesized without a signal peptide sequence and thus may remain sequestered in the cell (Basilico and Moscatelli, 1992;Cao and Pettersson, 1993). However, release of FGF may occur through leakage from damaged cells or from viable cells via a novel mechanism (Mignatti et al, 1992;Cao and Pettersson, 1993). Yeoman (1993) has postulated that proteoglycan-bound FGF may be released from the cell surface or extracellular matrix by the action of proteases, and Briozzo et al (1991) have shown that Received 10 June 1996 Revised 26 November 1996 Accepted 3 December 1996 Correspondence to: J Gomm MCF7 breast cancer cells secrete cathepsin D, which is able to digest the extracellular matrix and releas...

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“…There are at least four FGF receptor genes characterized by extracellular Ig-like loops and an intracellular tyrosine kinase (Johnson et al 1991, Partanen et al 1992. Moreover, there are many alternatively spliced transcripts, some of which encode secreted receptor sequences (Xu et al 1992).…”

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confidence: 99%

Molecular atherectomy for restenosis

Casscells

Lappi

Baird

1993

Trends in Cardiovascular Medicine

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Receptors for basic (b) and acidic (a) fibroblast growth factor (FGF) are upregulated in activated smooth muscle cells. These cells, which proliferate in response to bFGF, can thus be killed by a conjugate of bFGF and the ribosome-inactivating enzyme, saporin (which, by itself, does not enter the cells). Quiescent smooth muscle cells and other cells that have few FGF receptors are not killed. In vivo, bFGF-saporin transiently inhibits smooth muscle cell proliferation and neointimal accumulation after balloon injury to the rat carotid artery. Delivery of saporin, diagnostic imaging agents, or antisense oligodeoxynucleotides might be made even more selective by linking these substances to antibodies against the extracellular domains of the putative FGF receptor isoform specific for activated smooth muscle cells.

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Diverse receptors for fibroblast growth factors

Cited by 108 publications

References 60 publications

Phosphatidylinositol 3′-Kinase-independent p70 S6 Kinase Activation by Fibroblast Growth Factor Receptor-1 Is Important for Proliferation but Not Differentiation of Endothelial Cells

Phosphatidylinositol 3′-Kinase-independent p70 S6 Kinase Activation by Fibroblast Growth Factor Receptor-1 Is Important for Proliferation but Not Differentiation of Endothelial Cells

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue

Molecular atherectomy for restenosis

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