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Christin Carter-su - One of the best experts on this subject based on the ideXlab platform.
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The SH2-B Adaptor Protein Negatively Regulates EPO-Dependent Signalling Via Interaction with Erythropoietin Receptor Ptyr-343
Blood, 2008Co-Authors: Mojib Javadi Javed, Christin Carter-su, Edda Tschirch, Bryan K Beattie, Natalie Stickle, Kai Huang, Robert Jaster, Dwayne BarberAbstract:Erythropoiesis is a developmentally important process, whereby multipotent hematopoietic stem cells differentiate into mature erythrocytes. Erythropoietin (EPO) is a critical regulator in this process and mediates its signal via the erythropoietin receptor (EPO-R) and the primary associated tyrosine kinase, JAK2. EPO, EPO-R and JAK2 play a crucial role in erythropoiesis, as deficiency in any of these Proteins results in an embryonic lethal anemia. Structural-functional studies and murine knock-in models have shown EPO-R pTyr-343 to play a critical role in EPO mediated signalling. STAT-5 is activated by EPO-R pTyr-343, but STAT5 ΔN mice do not have any profound erythroid abnormalities. Such evidence has led our group to hypothesize that other SH2 containing effectors interact with EPO-R pTyr-343. Cloning of Ligand Target screening was utilized to demonstrate that EPO-R pTyr-343 binds to adaptor Protein SH2-Bβ. SH2-B contains multiple Protein-Protein interaction domains including multiple proline-rich regions, a PH domain and an SH2 domain. Although SH2-B does play a role in a number of signaling pathways, it is not required for embryonic development. Since SH2-B is a potent regulator of JAK2 in context of Growth Hormone and Leptin signaling, and it can directly interact with EPO-R pTyr-343, we hypothesize that SH2-B functions as an important adaptor Protein downstream of the EPO-R.H2-B constitutively associates to the inactive EPO-R, an interaction that is independent of JAK2 binding to the EPO-R. Upon EPO stimulation, enhanced SH2-dependent binding of SH2-B to pTyr-343 and pTyr-401 of the EPO-R was confirmed utilizing a panel of EPO-R truncation mutants. The EPO mediated interaction between SH2-B and activated EPO-R is both dose and time dependent. EPO stimulation also results in SH2-B serine and threonine phosphorylation. Importantly, the interaction of SH2-B and EPO-R was observed in erythroid cell lines and primary murine splenocytes. The function of SH2-B in EPO signaling was investigated via knocking down SH2-B in Ba/F3-EPO-R cells. Knock down of SH2-B results in hypersensitive EPO-dependent phosphorylation of multiple targets including the EPO-R, JAK2, STAT5 and Erk1/2. It is evident that SH2-B is a global negative regulator of EPO-dependent signaling via its ability to affect EPO-dependent JAK2 activation.
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Adapter Protein SH2-B Stimulates Actin-Based Motility of Listeria monocytogenes in a Vasodilator-Stimulated PhosphoProtein (VASP)-Dependent Fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Liangyou Rui, Christin Carter-suAbstract:SH2-Bbeta (Src homology 2 B) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bbeta is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bbeta localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B -/- mice. Both recruitment of SH2-Bbeta to Listeria and SH2-Bbeta stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bbeta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bbeta binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bbeta and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
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Capillary Electrophoresis and Fluorescence Anisotropy for Quantitative Analysis of Peptide−Protein Interactions Using JAK2 and SH2-Bβ as a Model System
Analytical chemistry, 2005Co-Authors: Peilin Yang, Christin Carter-su, Rebecca J. Whelan, Emily E. Jameson, Jason H. Kurzer, Lawrence S. Argetsinger, Abuzar Kabir, And Abdul Malik, Robert T. KennedyAbstract:Fluorescence anisotropy capillary electrophoresis (FACE) and affinity probe capillary electrophoresis (APCE) with laser-induced fluorescence detection were evaluated for analysis of peptide−Protein interactions with rapid binding kinetics. The Src homology 2 domain of Protein SH2-Bβ (SH2-Bβ (525−670)) and a tyrosine-phosphorylated peptide corresponding to the binding sequence of JAK2 were used as a model system. For peptide labeled with fluorescein, the Kd = 82 ± 7 nM as measured by fluorescence anisotropy (FA). APCE assays had a limit of detection (LOD) of 100 nM or 12 amol injected for SH2-Bβ (525−670). The separation time of 4 s, achieved using an electric field of 2860 V/cm on 7-cm-long capillaries, was on the same time scale as complex dissociation allowing Kd (101 ± 12 nM in good agreement with FA measurements) and dissociation rate (koff = 0.95 ± 0.02 s-1 corresponding to a half-life of 0.73 s) to be determined. This measurement represents a 30-fold higher rate of complex dissociation than what had...
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Tyrosine 813 Is a Site of JAK2 Autophosphorylation Critical for Activation of JAK2 by SH2-Bβ
Molecular and cellular biology, 2004Co-Authors: Jason H. Kurzer, Lawrence S. Argetsinger, Yong Jie Zhou, Jean-louis K. Kouadio, John J. O'shea, Christin Carter-suAbstract:The tyrosine kinase Janus kinase 2 (JAK2) binds to the majority of the known members of the cytokine family of receptors. Ligand-receptor binding leads to activation of the associated JAK2 molecules, resulting in rapid autophosphorylation of multiple tyrosines within JAK2. Phosphotyrosines can then serve as docking sites for downstream JAK2 signaling molecules. Despite the importance of these phosphotyrosines in JAK2 function, only a few sites and binding partners have been identified. Using two-dimensional phosphopeptide mapping and a phosphospecific antibody, we identified tyrosine 813 as a site of JAK2 autophosphorylation of overexpressed JAK2 and endogenous JAK2 activated by growth hormone. Tyrosine 813 is contained within a YXXL sequence motif associated with several other identified JAK2 phosphorylation sites. We show that phosphorylation of tyrosine 813 is required for the SH2 domain-containing adapter Protein SH2-Bβ to bind JAK2 and to enhance the activity of JAK2 and STAT5B. The homologous tyrosine in JAK3, tyrosine 785, is autophosphorylated in response to interleukin-2 stimulation and is required for SH2-Bβ to bind JAK3. Taken together these data strongly suggest that tyrosine 813 is a site of autophosphorylation in JAK2 and is the SH2-Bβ-binding site within JAK2 that is required for SH2-Bβ to enhance activation of JAK2.
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Adapter Protein SH2-Bβ Undergoes Nucleocytoplasmic Shuttling: Implications for Nerve Growth Factor Induction of Neuronal Differentiation
Molecular and cellular biology, 2004Co-Authors: Linyi Chen, Christin Carter-suAbstract:The adapter Protein SH2-B has been shown to bind to activated nerve growth factor (NGF) receptor TrkA and has been implicated in NGF-induced neuronal differentiation and the survival of sympathetic neurons. However, the mechanism by which SH2-B enhances and maintains neurite outgrowth is unclear. We examined the ability of truncation mutants to regulate neuronal differentiation and observed that certain truncation mutants localized in the nucleus rather than in the cytoplasm or at the plasma membrane as reported for wild-type SH2-Bβ. Addition of the nuclear export inhibitor leptomycin B caused both overexpressed wild-type and endogenous SH2-Bβ to accumulate in the nucleus of both PC12 cells and COS-7 cells as did deletion of a putative nuclear export sequence (amino acids 224 to 233) or mutation of two critical lysines in that sequence. Deleting or mutating the nuclear export signal caused SH2-Bβ to lose its ability to enhance NGF-induced differentiation of PC12 cells. Neither the NGF-induced phosphorylation of ERKs 1 and 2 nor their subcellular distribution was altered in PC12 cells stably expressing the nuclear export-defective SH2-Bβ(L231A, L233A). These data provide strong evidence that SH2-Bβ shuttles constitutively between the nucleus and cytoplasm. However, SH2-Bβ needs continuous access to the cytoplasm and/or plasma membrane to participate in NGF-induced neurite outgrowth. These data also suggest that the stimulatory effect of SH2-Bβ on NGF-induced neurite outgrowth of PC12 cells is either downstream of ERKs or via some other pathway yet to be identified.
Maria Diakonova - One of the best experts on this subject based on the ideXlab platform.
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adapter Protein SH2 bβ stimulates actin based motility of listeria monocytogenes in a vasodilator stimulated phosphoProtein vasp dependent fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Christin CartersuAbstract:SH2-Bβ (Src homology 2 Bβ) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bβ is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bβ localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B−/− mice. Both recruitment of SH2-Bβ to Listeria and SH2-Bβ stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bβ enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bβ binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bβ and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
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Adapter Protein SH2-B Stimulates Actin-Based Motility of Listeria monocytogenes in a Vasodilator-Stimulated PhosphoProtein (VASP)-Dependent Fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Liangyou Rui, Christin Carter-suAbstract:SH2-Bbeta (Src homology 2 B) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bbeta is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bbeta localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B -/- mice. Both recruitment of SH2-Bbeta to Listeria and SH2-Bbeta stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bbeta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bbeta binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bbeta and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
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SH2-Bβ Is a Rac-binding Protein That Regulates Cell Motility
The Journal of biological chemistry, 2002Co-Authors: Maria Diakonova, David R. Gunter, James Herrington, Christin Carter-suAbstract:Abstract The Src homology 2 (SH2) domain-containing Protein SH2-Bβ binds to and is a substrate of the growth hormone (GH) and cytokine receptor-associated tyrosine kinase JAK2. SH2-Bβ also binds, via its SH2 domain, to multiple activated growth factor receptor tyrosine kinases. We have previously implicated SH2-Bβ in GH and platelet-derived growth factor regulation of the actin cytoskeleton. We extend these findings by establishing a potentiating effect of SH2-Bβ on GH-dependent cell motility and defining regions of SH2-Bβ required for this potentiation. Time-lapse video microscopy, phagokinetic, and/or wounding assays demonstrate reduced movement of cells overexpressing SH2-Bβ lacking an intact SH2 domain because of a point mutation or a C-terminal truncation. An N-terminal proline-rich domain (amino acids 85–106) of SH2-Bβ is required for inhibition of cellular motility by SH2 domain-deficient mutants. Co-immunoprecipitation experiments indicate that Rac binds to this domain. GH is shown to activate endogenous Rac, and dominant negative mutants of SH2-Bβ are shown to inhibit membrane ruffling induced by constitutively active Rac. These findings suggest that SH2-Bβ is an adapter Protein that facilitates actin rearrangement and cellular motility by recruiting Rac and potentially Rac-regulating, Rac effector, or other actin-regulating Proteins to activated cytokine (e.g. GH) and growth factor receptors.
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SH2-B Is Required for Growth Hormone-induced Actin Reorganization
The Journal of biological chemistry, 2000Co-Authors: James Herrington, Maria Diakonova, Liangyou Rui, David R. Gunter, Christin Carter-suAbstract:The Src homology-2 (SH2) domain-containing Protein SH2-Bbeta is a substrate of the growth hormone (GH) receptor-associated tyrosine kinase JAK2. Here we tested whether SH2-Bbeta is involved in GH regulation of the actin cytoskeleton. Based on cell fractionation and confocal microscopy, we find SH2-Bbeta present at the plasma membrane and in the cytosol. SH2-Bbeta colocalized with filamentous actin in GH and platelet-derived growth factor (PDGF)-induced membrane ruffles. To test if SH2-Bbeta is required for actin reorganization, we transiently overexpressed wild-type or mutant SH2-Bbeta in 3T3-F442A cells and assayed for GH- and PDGF-induced membrane ruffling and fluid phase pinocytosis. Overexpression of wild-type SH2-Bbeta enhanced ruffling and pinocytosis produced by submaximal GH but not submaximal PDGF. Point mutant SH2-Bbeta (R555E) and truncation mutant DeltaC555, both lacking a functional SH2 domain, inhibited membrane ruffling and pinocytosis induced by GH and PDGF. Mutant DeltaN504, which possesses a functional SH2 domain and enhances JAK2 kinase activity in overexpression systems, also inhibited GH-stimulated membrane ruffling. DeltaN504 failed to inhibit GH-induced nuclear localization of Stat5B, indicating JAK2 is active in these cells. Taken together, these results show that SH2-Bbeta is required for GH-induced actin reorganization by a mechanism discrete from the action of SH2-Bbeta as a stimulator of JAK2 kinase activity.
Christin Cartersu - One of the best experts on this subject based on the ideXlab platform.
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adapter Protein SH2 bβ stimulates actin based motility of listeria monocytogenes in a vasodilator stimulated phosphoProtein vasp dependent fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Christin CartersuAbstract:SH2-Bβ (Src homology 2 Bβ) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bβ is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bβ localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B−/− mice. Both recruitment of SH2-Bβ to Listeria and SH2-Bβ stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bβ enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bβ binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bβ and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
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capillary electrophoresis and fluorescence anisotropy for quantitative analysis of peptide Protein interactions using jak2 and SH2 bβ as a model system
Analytical Chemistry, 2005Co-Authors: Peilin Yang, Christin Cartersu, Rebecca J. Whelan, Emily E. Jameson, Jason H. Kurzer, Lawrence S. Argetsinger, Abuzar Kabir, And Abdul Malik, Robert T. KennedyAbstract:Fluorescence anisotropy capillary electrophoresis (FACE) and affinity probe capillary electrophoresis (APCE) with laser-induced fluorescence detection were evaluated for analysis of peptide−Protein interactions with rapid binding kinetics. The Src homology 2 domain of Protein SH2-Bβ (SH2-Bβ (525−670)) and a tyrosine-phosphorylated peptide corresponding to the binding sequence of JAK2 were used as a model system. For peptide labeled with fluorescein, the Kd = 82 ± 7 nM as measured by fluorescence anisotropy (FA). APCE assays had a limit of detection (LOD) of 100 nM or 12 amol injected for SH2-Bβ (525−670). The separation time of 4 s, achieved using an electric field of 2860 V/cm on 7-cm-long capillaries, was on the same time scale as complex dissociation allowing Kd (101 ± 12 nM in good agreement with FA measurements) and dissociation rate (koff = 0.95 ± 0.02 s-1 corresponding to a half-life of 0.73 s) to be determined. This measurement represents a 30-fold higher rate of complex dissociation than what had...
Liangyou Rui - One of the best experts on this subject based on the ideXlab platform.
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Adapter Protein SH2-B Stimulates Actin-Based Motility of Listeria monocytogenes in a Vasodilator-Stimulated PhosphoProtein (VASP)-Dependent Fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Liangyou Rui, Christin Carter-suAbstract:SH2-Bbeta (Src homology 2 B) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bbeta is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bbeta localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B -/- mice. Both recruitment of SH2-Bbeta to Listeria and SH2-Bbeta stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bbeta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bbeta binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bbeta and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
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SH2-B Is Required for Growth Hormone-induced Actin Reorganization
The Journal of biological chemistry, 2000Co-Authors: James Herrington, Maria Diakonova, Liangyou Rui, David R. Gunter, Christin Carter-suAbstract:The Src homology-2 (SH2) domain-containing Protein SH2-Bbeta is a substrate of the growth hormone (GH) receptor-associated tyrosine kinase JAK2. Here we tested whether SH2-Bbeta is involved in GH regulation of the actin cytoskeleton. Based on cell fractionation and confocal microscopy, we find SH2-Bbeta present at the plasma membrane and in the cytosol. SH2-Bbeta colocalized with filamentous actin in GH and platelet-derived growth factor (PDGF)-induced membrane ruffles. To test if SH2-Bbeta is required for actin reorganization, we transiently overexpressed wild-type or mutant SH2-Bbeta in 3T3-F442A cells and assayed for GH- and PDGF-induced membrane ruffling and fluid phase pinocytosis. Overexpression of wild-type SH2-Bbeta enhanced ruffling and pinocytosis produced by submaximal GH but not submaximal PDGF. Point mutant SH2-Bbeta (R555E) and truncation mutant DeltaC555, both lacking a functional SH2 domain, inhibited membrane ruffling and pinocytosis induced by GH and PDGF. Mutant DeltaN504, which possesses a functional SH2 domain and enhances JAK2 kinase activity in overexpression systems, also inhibited GH-stimulated membrane ruffling. DeltaN504 failed to inhibit GH-induced nuclear localization of Stat5B, indicating JAK2 is active in these cells. Taken together, these results show that SH2-Bbeta is required for GH-induced actin reorganization by a mechanism discrete from the action of SH2-Bbeta as a stimulator of JAK2 kinase activity.
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Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling.
Molecular and cellular biology, 1997Co-Authors: Liangyou Rui, L S Mathews, K Hotta, T A Gustafson, Christin Carter-suAbstract:Activation of the tyrosine kinase JAK2 is an essential step in cellular signaling by growth hormone (GH) and multiple other hormones and cytokines. Murine JAK2 has a total of 49 tyrosines which, if phosphorylated, could serve as docking sites for Src homology 2 (SH2) or phosphotyrosine binding domain-containing signaling molecules. Using a yeast two-hybrid screen of a rat adipocyte cDNA library, we identified a splicing variant of the SH2 domain-containing Protein SH2-B, designated SH2-Bbeta, as a JAK2-interacting Protein. The carboxyl terminus of SH2-Bbeta (SH2-Bbetac), which contains the SH2 domain, specifically interacts with kinase-active, tyrosyl-phosphorylated JAK2 but not kinase-inactive, unphosphorylated JAK2 in the yeast two-hybrid system. In COS cells coexpressing SH2-Bbeta or SH2-Bbetac and murine JAK2, both SH2-Bbetac and SH2-Bbeta coimmunoprecipitate to a significantly greater extent with wild-type, tyrosyl-phosphorylated JAK2 than with kinase-inactive, unphosphorylated JAK2. SH2-Bbetac also binds to immunoprecipitated wild-type but not kinase-inactive JAK2 in a far Western blot. In 3T3-F442A cells, GH stimulates the interaction of SH2-Bbeta with tyrosyl-phosphorylated JAK2 both in vitro, as assessed by binding of JAK2 in cell lysates to glutathione S-transferase (GST)-SH2-Bbetac or GST-SH2-Bbeta fusion Proteins, and in vivo, as assessed by coimmunoprecipitation of JAK2 with SH2-Bbeta. GH promoted a transient and dose-dependent tyrosyl phosphorylation of SH2-Bbeta in 3T3-F442A cells, further suggesting the involvement of SH2-Bbeta in GH signaling. Consistent with SH2-Bbeta being a substrate of JAK2, SH2-Bbetac is tyrosyl phosphorylated when coexpressed with wild-type but not kinase-inactive JAK2 in both yeast and COS cells. SH2-Bbeta was also tyrosyl phosphorylated in response to gamma interferon, a cytokine that activates JAK2 and JAK1. These data suggest that GH-induced activation and phosphorylation of JAK2 recruits SH2-Bbeta and its associated signaling molecules into a GHR-JAK2 complex, thereby initiating some as yet unidentified signal transduction pathways. These pathways are likely to be shared by other cytokines that activate JAK2.
Marie-france Carlier - One of the best experts on this subject based on the ideXlab platform.
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adapter Protein SH2 bβ stimulates actin based motility of listeria monocytogenes in a vasodilator stimulated phosphoProtein vasp dependent fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Christin CartersuAbstract:SH2-Bβ (Src homology 2 Bβ) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bβ is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bβ localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B−/− mice. Both recruitment of SH2-Bβ to Listeria and SH2-Bβ stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bβ enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bβ binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bβ and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
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Adapter Protein SH2-B Stimulates Actin-Based Motility of Listeria monocytogenes in a Vasodilator-Stimulated PhosphoProtein (VASP)-Dependent Fashion
Infection and Immunity, 2007Co-Authors: Maria Diakonova, Emmanuele Helfer, Christine Kocks, Stephanie Seveau, Joel A. Swanson, Marie-france Carlier, Liangyou Rui, Christin Carter-suAbstract:SH2-Bbeta (Src homology 2 B) is an adapter Protein that is required for maximal growth hormone-dependent actin reorganization in membrane ruffling and cell motility. Here we show that SH2-Bbeta is also required for maximal actin-based motility of Listeria monocytogenes. SH2-Bbeta localizes to Listeria-induced actin tails and increases the rate of bacterial propulsion in infected cells and in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo fibroblasts from SH2-B -/- mice. Both recruitment of SH2-Bbeta to Listeria and SH2-Bbeta stimulation of actin-based propulsion require the vasodilator-stimulated phosphoProtein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bacterial actin-based motility. SH2-Bbeta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility assay, provided that VASP is present. In vitro binding assays show that SH2-Bbeta binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP. Because VASP also plays an essential regulatory role in actin-based processes in eukaryotic cells, the present results provide mechanistic insight into the functions of both SH2-Bbeta and VASP in motility and also increase our understanding of the fundamental mechanism by which Listeria spreads.
