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Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated in the regulation of cell growth and actin rearrangement mediated by several receptor tyrosine kinases, including platelet-derived growth factor and epidermal growth factor. Here we identify the Xenopus laevis homolog of LMW-PTP1 (XLPTP1) as an additional positive regulator in the fibroblast growth factor (FGF) signaling pathway during Xenopus development. XLPTP1 has an expression pattern that displays substantial overlap with FGF receptor 1 (FGFR1) during Xenopus development. Using morpholino antisense technology, we show that inhibition of endogenous XLPTP1 expression dramatically restricts anterior and posterior structure development and inhibits mesoderm formation. In ectodermal explants, loss of XLPTP1 expression dramatically blocks the induction of the early mesoderm gene, Xbrachyury (Xbra), by FGF and partially blocks Xbra induction by Activin. Moreover, FGF-induced activation of mitogen-activated protein (MAP) kinase is also inhibited by XLPTP1 morpholino antisense oligonucleotides; however, introduction of RNA encoding XLPTP1 is able to rescue morphological and biochemical effects of antisense inhibition. Inhibition of FGF-induced MAP kinase activity due to loss of XLPTP1 is also rescued by an active Ras, implying that XLPTP1 may act upstream of or parallel to Ras. Finally, XLPTP1 physically associates only with an activated FGFR1, and this interaction requires the presence of SNT1/FRS-2 (FGFR substrate 2). Although LMW-PTP1 has been shown to participate in other receptor systems, the data presented here also reveal XLPTP1 as a new and important component of the FGF signaling pathway.
Akagi,
Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling during Xenopus embryonic development.
2002, Pubmed,
Xenbase
Akagi,
Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling during Xenopus embryonic development.
2002,
Pubmed
,
Xenbase Amaya,
Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos.
1991,
Pubmed
,
Xenbase Amaya,
FGF signalling in the early specification of mesoderm in Xenopus.
1993,
Pubmed
,
Xenbase Ataliotis,
PDGF signalling is required for gastrulation of Xenopus laevis.
1995,
Pubmed
,
Xenbase Barrett,
The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation.
1997,
Pubmed Brivanlou,
Expression of an engrailed-related protein is induced in the anterior neural ectoderm of early Xenopus embryos.
1989,
Pubmed
,
Xenbase Bucciantini,
Sequence-specific recognition of peptide substrates by the low Mr phosphotyrosine protein phosphatase isoforms.
1998,
Pubmed Carballada,
Phosphatidylinositol-3 kinase acts in parallel to the ERK MAP kinase in the FGF pathway during Xenopus mesoderm induction.
2001,
Pubmed
,
Xenbase Casci,
Sprouty, an intracellular inhibitor of Ras signaling.
1999,
Pubmed Chiarugi,
PDGF receptor as a specific in vivo target for low M(r) phosphotyrosine protein phosphatase.
1995,
Pubmed Chiarugi,
Low M(r) phosphotyrosine protein phosphatase interacts with the PDGF receptor directly via its catalytic site.
1996,
Pubmed Chiarugi,
The low M(r) protein-tyrosine phosphatase is involved in Rho-mediated cytoskeleton rearrangement after integrin and platelet-derived growth factor stimulation.
2000,
Pubmed Chong,
Fibroblast growth factor receptor-mediated rescue of x-ephrin B1-induced cell dissociation in Xenopus embryos.
2000,
Pubmed
,
Xenbase Christen,
Spatial response to fibroblast growth factor signalling in Xenopus embryos.
1999,
Pubmed
,
Xenbase Cirri,
Low molecular weight protein-tyrosine phosphatase tyrosine phosphorylation by c-Src during platelet-derived growth factor-induced mitogenesis correlates with its subcellular targeting.
1998,
Pubmed Cirri,
The molecular basis of the differing kinetic behavior of the two low molecular mass phosphotyrosine protein phosphatase isoforms.
1996,
Pubmed Cossette,
Localization and down-regulating role of the protein tyrosine phosphatase PTP2C in membrane ruffles of PDGF-stimulated cells.
1996,
Pubmed Curran,
Expression of activated MAP kinase in Xenopus laevis embryos: evaluating the roles of FGF and other signaling pathways in early induction and patterning.
2000,
Pubmed
,
Xenbase Dissing,
Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles.
1992,
Pubmed Dissing,
Human red cell acid phosphatase (ACP1). The amino acid sequence of the two isozymes Bf and Bs encoded by the ACP1*B allele.
1991,
Pubmed Fabian,
Requirement for Raf and MAP kinase function during the meiotic maturation of Xenopus oocytes.
1993,
Pubmed
,
Xenbase Fauman,
Structure and function of the protein tyrosine phosphatases.
1996,
Pubmed Fürthauer,
Sef is a feedback-induced antagonist of Ras/MAPK-mediated FGF signalling.
2002,
Pubmed Golub,
Evolutionarily conserved and divergent expression of members of the FGF receptor family among vertebrate embryos, as revealed by FGFR expression patterns in Xenopus.
2000,
Pubmed
,
Xenbase Gotoh,
Involvement of the MAP kinase cascade in Xenopus mesoderm induction.
1995,
Pubmed
,
Xenbase Graves,
Fibroblast growth factor, but not activin, is a potent activator of mitogen-activated protein kinase in Xenopus explants.
1994,
Pubmed
,
Xenbase Green,
Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate.
1990,
Pubmed
,
Xenbase Gupta,
Dominant-negative mutants of the SH2/SH3 adapters Nck and Grb2 inhibit MAP kinase activation and mesoderm-specific gene induction by eFGF in Xenopus.
1998,
Pubmed
,
Xenbase Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase Hartley,
MAP kinase is activated during mesoderm induction in Xenopus laevis.
1994,
Pubmed
,
Xenbase Heasman,
Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach.
2000,
Pubmed
,
Xenbase Hemmati-Brivanlou,
Inhibition of activin receptor signaling promotes neuralization in Xenopus.
1994,
Pubmed
,
Xenbase Hemmati-Brivanlou,
A truncated activin receptor inhibits mesoderm induction and formation of axial structures in Xenopus embryos.
1992,
Pubmed
,
Xenbase Hunter,
Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling.
1995,
Pubmed Isaacs,
eFGF regulates Xbra expression during Xenopus gastrulation.
1994,
Pubmed
,
Xenbase Joukov,
Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development.
2001,
Pubmed
,
Xenbase Keller,
Early embryonic development of Xenopus laevis.
1991,
Pubmed
,
Xenbase Kimelman,
Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo.
1987,
Pubmed
,
Xenbase Kouhara,
A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway.
1997,
Pubmed Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase LaBonne,
Localization of MAP kinase activity in early Xenopus embryos: implications for endogenous FGF signaling.
1997,
Pubmed
,
Xenbase LaBonne,
Mesoderm induction by activin requires FGF-mediated intracellular signals.
1994,
Pubmed
,
Xenbase LaBonne,
Role of MAP kinase in mesoderm induction and axial patterning during Xenopus development.
1995,
Pubmed
,
Xenbase Landgren,
Fibroblast growth factor receptor-1 regulation of Src family kinases.
1995,
Pubmed Larsson,
Fibroblast growth factor receptor-1-mediated endothelial cell proliferation is dependent on the Src homology (SH) 2/SH3 domain-containing adaptor protein Crk.
1999,
Pubmed Lazaruk,
Exon structure at the human ACP1 locus supports alternative splicing model for f and s isozyme generation.
1993,
Pubmed Lechleider,
Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor.
1993,
Pubmed MacNicol,
Raf-1 kinase is essential for early Xenopus development and mediates the induction of mesoderm by FGF.
1993,
Pubmed
,
Xenbase Maeda,
Xmeis1, a protooncogene involved in specifying neural crest cell fate in Xenopus embryos.
2001,
Pubmed
,
Xenbase Magherini,
Cloning of murine low molecular weight phosphotyrosine protein phosphatase cDNA: identification of a new isoform.
1998,
Pubmed Manao,
Rat liver low M(r) phosphotyrosine protein phosphatase isoenzymes: purification and amino acid sequences.
1992,
Pubmed Mayor,
Induction of the prospective neural crest of Xenopus.
1995,
Pubmed
,
Xenbase Modesti,
Cloning, expression and characterisation of a new human low Mr phosphotyrosine protein phosphatase originating by alternative splicing.
1998,
Pubmed Mohammadi,
A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1.
1991,
Pubmed Muslin,
Direct activation of phospholipase C-gamma by fibroblast growth factor receptor is not required for mesoderm induction in Xenopus animal caps.
1994,
Pubmed
,
Xenbase Nasevicius,
Effective targeted gene 'knockdown' in zebrafish.
2000,
Pubmed Neilson,
Ligand-independent activation of fibroblast growth factor receptors by point mutations in the extracellular, transmembrane, and kinase domains.
1996,
Pubmed
,
Xenbase Nutt,
Xenopus Sprouty2 inhibits FGF-mediated gastrulation movements but does not affect mesoderm induction and patterning.
2001,
Pubmed
,
Xenbase Ong,
FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors.
2000,
Pubmed Ong,
Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins.
2001,
Pubmed O'Reilly,
Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps.
2000,
Pubmed
,
Xenbase Powers,
Fibroblast growth factors, their receptors and signaling.
2000,
Pubmed Ramponi,
The 18 kDa cytosolic acid phosphatase from bovine live has phosphotyrosine phosphatase activity on the autophosphorylated epidermal growth factor receptor.
1989,
Pubmed Ramponi,
Structural, catalytic, and functional properties of low M(r), phosphotyrosine protein phosphatases. Evidence of a long evolutionary history.
1997,
Pubmed Ramponi,
Structure and function of the low Mr phosphotyrosine protein phosphatases.
1997,
Pubmed Richter,
A developmentally regulated, nervous system-specific gene in Xenopus encodes a putative RNA-binding protein.
1990,
Pubmed
,
Xenbase Rönnstrand,
Mechanisms of platelet-derived growth factor-induced chemotaxis.
2001,
Pubmed Rönnstrand,
SHP-2 binds to Tyr763 and Tyr1009 in the PDGF beta-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis.
1999,
Pubmed Rovida,
The low-molecular-weight phosphotyrosine protein phosphatase, when overexpressed, reduces the mitogenic response to macrophage colony-stimulating factor and tyrosine phosphorylation of its receptor.
1998,
Pubmed Rudbeck,
Human 18 kDa phosphotyrosine protein phosphatase (ACP1) polymorphism: studies of rare variants provide evidence that substitutions within or near alternatively spliced exons affect splicing result.
2000,
Pubmed Schulte-Merker,
Mesoderm formation in response to Brachyury requires FGF signalling.
1995,
Pubmed
,
Xenbase Slack,
Mesoderm induction in early Xenopus embryos by heparin-binding growth factors.
,
Pubmed
,
Xenbase Stein,
Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses.
1998,
Pubmed Stone,
Protein-tyrosine phosphatases.
1994,
Pubmed Summerton,
Morpholino antisense oligomers: the case for an RNase H-independent structural type.
1999,
Pubmed Taddei,
LMW-PTP exerts a differential regulation on PDGF- and insulin-mediated signaling.
2000,
Pubmed Tailor,
A novel isoform of the low molecular weight phosphotyrosine phosphatase, LMPTP-C, arising from alternative mRNA splicing.
1999,
Pubmed Tang,
The SH2-containing protein-tyrosine phosphatase SH-PTP2 is required upstream of MAP kinase for early Xenopus development.
1995,
Pubmed
,
Xenbase Tapon,
Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.
1997,
Pubmed Tsang,
Identification of Sef, a novel modulator of FGF signalling.
2002,
Pubmed
,
Xenbase Umbhauer,
Mesoderm induction in Xenopus caused by activation of MAP kinase.
1995,
Pubmed
,
Xenbase Vincent,
The Drosophila protein Dof is specifically required for FGF signaling.
1998,
Pubmed Wang,
Crystal structures of a low-molecular weight protein tyrosine phosphatase from Saccharomyces cerevisiae and its complex with the substrate p-nitrophenyl phosphate.
2000,
Pubmed Weinstein,
FGF-mediated mesoderm induction involves the Src-family kinase Laloo.
1998,
Pubmed
,
Xenbase Whitman,
Involvement of p21ras in Xenopus mesoderm induction.
1992,
Pubmed
,
Xenbase Winning,
Developmental regulation of transcription factor AP-2 during Xenopus laevis embryogenesis.
1991,
Pubmed
,
Xenbase Wo,
Cloning, expression, and catalytic mechanism of the low molecular weight phosphotyrosyl protein phosphatase from bovine heart.
1992,
Pubmed Zhan,
Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin.
1994,
Pubmed