Regulation of FGF Receptors in the Oligodendrocyte Lineage

Bansal, Rashmi; Kumar, Mythri Anil; Murray, Kerren; Morrison, Richard S.; Pfeiffer, S. E.

doi:10.1006/mcne.1996.0020

Cited by 167 publications

(216 citation statements)

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“…The low mitogenic response of FGFR3 to FGF2 is consistent with the results of a previous study using BaF3 cells expressing the mouse full-length FGFR3 (11). It has also been reported that a soluble FGFR3c did not bind to FGF2 but bound to FGF1 (36).…”

Section: Gene Expression and Biological Roles Of Fgfrs Insupporting

confidence: 90%

“…FGFRs lacking IgI have a higher ligand affinity for some FGF ligands, although it is not known if ligand binding specificity is affected by removal of the IgI domain (6). Distinct expression patterns of these isoforms have also been reported in cell differentiation (11), embryonal development (12), and tumor progression (13), suggesting that there are functional differences between these isoforms.…”

mentioning

confidence: 97%

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A Novel Alternatively Spliced Fibroblast Growth Factor Receptor 3 Isoform Lacking the Acid Box Domain Is Expressed during Chondrogenic Differentiation of ATDC5 Cells

Shimizu

Tada

Shukunami

et al. 2001

Journal of Biological Chemistry

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To determine the role of fibroblast growth factor (FGF)⅐FGF receptor (FGFR) signaling in chondrogenesis, we analyzed the gene expression of alternatively spliced FGFRs during chondrogenic differentiation of ATDC5 cells in vitro. Two isoforms of FGFR3 were expressed in these cells. One was the complete form of FGFR3 (FGFR3) already reported, and the other was a novel one that lacks the acid box domain (FGFR3⌬AB). The gene of FGFR3⌬AB was expressed in undifferentiated ATDC5 cells. In contrast, the transcripts of FGFR3 were not detectable in undifferentiated cells but increased during cellular condensation, which is an obligatory step for chondrogenic differentiation. FGFR1 and FGFR2 expression was higher than that of FGFR3 in undifferentiated cells. The gene expression of cell cycle inhibitor p21 was induced during cell condensation and correlated best with the expression of FGFR3 among the FGFR isoforms expressed. The differential expression of FGFR3 isoforms during chondrogenesis suggests that these isoforms may play different roles in the regulation of growth and differentiation in chondrocytes. To define the mitogenic response of FGFR3⌬AB and FGFR3 to FGFs, their cDNAs were stably transfected into mouse BaF3 pro-B cells. FGFR3 preferentially mediates the mitogenic response to FGF1 and poor response to FGF2. In contrast, FGFR3⌬AB mediated a higher mitogenic response to FGF2 as well as to FGF1. In addition, FGFR3⌬AB responds to FGF1 at lower concentrations of heparin than FGFR3 does. These results suggest that the acid box plays an important role in the regulation of FGFR3 to mediate biological activities in response to FGFs.

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Section: Gene Expression and Biological Roles Of Fgfrs Insupporting

confidence: 90%

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confidence: 97%

A Novel Alternatively Spliced Fibroblast Growth Factor Receptor 3 Isoform Lacking the Acid Box Domain Is Expressed during Chondrogenic Differentiation of ATDC5 Cells

Shimizu

Tada

Shukunami

et al. 2001

Journal of Biological Chemistry

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“…PD173074 (1-tert-butyl-3-[6-(3,5- Cell culture. Purified populations of OL progenitors and mature OLs were prepared, and their purity and phenotype were characterized by immunolabeling with a panel of antibodies as described previously (Bansal et al, 1996;Bansal and Pfeiffer, 1997). Briefly, early progenitors were obtained from mixed primary cultures from neonatal rat telencephalon (postnatal days 1-2) by overnight shaking, followed by differential adhesion and complement lysis with anti-galactocerebroside (GalC).…”

Section: Methodsmentioning

confidence: 99%

“…Live cells were immunolabeled as described previously (Bansal et al, 1996). Briefly, cells were blocked for nonspecific absorption with HEPES-buffered Earl's balanced salt solution (EBSS-HEPES) containing 3% normal goat serum (also used for diluting antibodies), double immunolabeled with OL lineage stagespecific markers [early progenitors, A2B5; late progenitors, O4; mature OLs, anti-GalC/sulfatide (R-mAb) or anti-myelin basic protein (MBP) (Sternberger Monoclonals, Lutherville, MD)].…”

Section: Methodsmentioning

confidence: 99%

Distinct Fibroblast Growth Factor (FGF)/FGF Receptor Signaling Pairs Initiate Diverse Cellular Responses in the Oligodendrocyte Lineage

Fortin¹,

Rom²,

Sun³

et al. 2005

J. Neurosci.

144

166

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Fibroblast growth factors (FGFs) have been implicated in numerous cellular processes, including proliferation, migration, differentiation, and survival. Whereas FGF-2, the prototypic ligand in a family of 22 members, activates all four tyrosine kinase FGF receptors (FGFR1-FGFR4), other members demonstrate a higher degree of selectivity. Oligodendrocytes (OLs), the myelin-producing cells of the CNS, are highly influenced by FGF-2 at all stages of their development. However, how other FGFs and their cognate receptors orchestrate the development of OLs is essentially undefined. Using a combination of specific FGF ligands and receptor blocking antibodies, we now show that FGF-8 and FGF-17 target OL progenitors, inhibiting their terminal differentiation via the activation of FGFR3, whereas FGF-9 specifically targets differentiated OLs, triggering increases in process growth via FGFR2 signaling; FGF-18 targets both OL progenitors and OLs via activation of both FGFR2 and FGFR3. These events are highly correlated with changes in FGF receptor expression from FGFR3 to FGFR2 as OL progenitors differentiate into mature OLs. In addition, we demonstrate that, although activation of FGFR1 by FGF-2 leads to proliferation of OL progenitors, it produces deleterious effects on differentiated OLs (i.e., aberrant reentry into cell cycle and downregulation of myelin proteins with a loss of myelin membrane). These data suggest that ligand availability, coupled with changes in FGF receptor expression, yield a changing repertoire of ligand-receptor signaling complexes that contribute critically to the regulation of both normal OL development and potential OL/myelin pathogenesis.

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“…Specificity can be achieved temporally by the developmentally regulated expression of certain components of the pathways. For instance, the expression of different FGFR types is regulated during oligodendrocyte maturation, providing a molecular basis for the developmentally varying response of cells to a common ligand (16). Specificity can also originate from the type of receptor expressed, because all of the FGFRs do not appear to have the same efficiency at activating various downstream pathways (17)(18)(19).…”

mentioning

confidence: 99%

Fibroblast Growth Factor-2-induced Signaling through Lipid Raft-associated Fibroblast Growth Factor Receptor Substrate 2 (FRS2)

Ridyard¹,

Robbins

2003

Journal of Biological Chemistry

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The plasma membrane is not homogenous but contains specific subcompartments characterized by their unique lipid and protein composition. Based on their enrichment in various signaling molecules, these membrane microdomains are recognized to be sites of localized signal transduction for a number of extracellular stimuli. We have previously shown that fibroblast growth factor-2 (FGF2) induced a specific signaling response within a lipid raft membrane microdomain in human neuroblastoma cells characterized by the tyrosine phosphorylation of a p80 phosphoprotein. Herein, we show that this protein is the signaling adaptor FRS2 and that it is localized exclusively to lipid rafts in vitro and in vivo. We have examined how the tyrosine phosphorylation and serine-threonine phosphorylation of FRS2 within lipid rafts affect the response of cells to FGF2 signaling. Our data suggest that activation of protein kinase C, Src family kinases, and MEK1/2 are involved in regulating serine-threonine phosphorylation of FRS2, which can indirectly affect FRS2 phosphotyrosine levels. We also show that Grb2 is recruited to lipid rafts during signaling events and that activation of MEK1/2 by different mechanisms within lipid rafts may lead to different cellular responses. This work suggests that compartmentalized signaling within lipid rafts may provide a level of specificity for growth factor signaling.

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Regulation of FGF Receptors in the Oligodendrocyte Lineage

Cited by 167 publications

References 0 publications

A Novel Alternatively Spliced Fibroblast Growth Factor Receptor 3 Isoform Lacking the Acid Box Domain Is Expressed during Chondrogenic Differentiation of ATDC5 Cells

A Novel Alternatively Spliced Fibroblast Growth Factor Receptor 3 Isoform Lacking the Acid Box Domain Is Expressed during Chondrogenic Differentiation of ATDC5 Cells

Distinct Fibroblast Growth Factor (FGF)/FGF Receptor Signaling Pairs Initiate Diverse Cellular Responses in the Oligodendrocyte Lineage

Fibroblast Growth Factor-2-induced Signaling through Lipid Raft-associated Fibroblast Growth Factor Receptor Substrate 2 (FRS2)

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