Research Topics
Genomes and Genes | Melanie J WelhamSummaryAffiliation: University of Bath Country: UK Publications
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Publications
Controlling embryonic stem cell proliferation and pluripotency: the role of PI3K- and GSK-3-dependent signallingMelanie J Welham
Centre for Regenerative Medicine, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
Biochem Soc Trans 39:674-8. 2011....
Tyrosine phosphatase SHP-1 acts at different stages of development to regulate hematopoiesisNicholas R D Paling
Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY United Kingdom
Blood 105:4290-7. 2005....
Insulin receptor substrate-2 is the major 170-kDa protein phosphorylated on tyrosine in response to cytokines in murine lymphohemopoietic cellsM J Welham
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada
J Biol Chem 272:1377-81. 1997....
Phosphoinositide 3-kinases and regulation of embryonic stem cell fateM J Welham
Department of Pharmacy and Pharmacology and The Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, UK
Biochem Soc Trans 35:225-8. 2007..In the present paper, we review the evidence that PI3K (phosphoinositide 3-kinase)-dependent signalling plays a role in regulation of both ES cell pluripotency and proliferation...
Regulation of interleukin-3-induced substrate phosphorylation and cell survival by SHP-2 (Src-homology protein tyrosine phosphatase 2)Helen Wheadon
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
Biochem J 376:147-57. 2003..These findings indicate that SHP-2 plays an important role in mediating the anti-apoptotic effect of IL-3 and raises the possibility that PECAM-1 participates in the modulation of cytokine-induced signals...
Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signalingNicholas R D Paling
Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
J Biol Chem 279:48063-70. 2004..Our studies support a role for PI3Ks in regulation of self-renewal and increase our understanding of the molecular signaling components involved in regulation of stem cell fate...
Ligation of CD28 stimulates the formation of a multimeric signaling complex involving grb-2-associated binder 2 (gab2), SRC homology phosphatase-2, and phosphatidylinositol 3-kinase: evidence that negative regulation of CD28 signaling requires the gab2 plRichard V Parry
Lymphocyte Activation Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
J Immunol 176:594-602. 2006..Furthermore, the inhibitory capacity of Gab2 is strictly dependent upon the integrity of its PH domain, suggesting phosphoinositide-mediated membrane recruitment is important to Gab2 function in T cells...
Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesisHeather K Bone
Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY, UK
J Cell Sci 120:1752-62. 2007..These data demonstrate that PI3K-dependent signals play important roles at different stages of haemopoietic development...
The coupling of TEL/PDGFbetaR to distinct functional responses is modulated by the presence of cytokine: involvement of mitogen-activated protein kinasesHelen Wheadon
Department of Pharmacy and Pharmacology, University of Bath, United Kingdom
Blood 102:1480-9. 2003..Given that in vivo hematopoietic cells are in contact with a variety of cytokines, our results have important implications for cellular responses in the pathogenesis of CMML...
Role of the protein tyrosine phosphatase SHP-1 (Src homology phosphatase-1) in the regulation of interleukin-3-induced survival, proliferation and signallingNicholas R D Paling
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
Biochem J 368:885-94. 2002..These results demonstrate that SHP-1 acts to negatively regulate IL-3-driven survival and proliferation, potentially via regulation of tyrosine phosphorylation of Aic2A and STAT5...
The pleckstrin homology domain of Gab-2 is required for optimal interleukin-3 signalsome-mediated responsesChristine E Edmead
Department of Pharmacy and Pharmacology, The University of Bath, Bath, BA2 7AY, UK
Cell Signal 18:1147-55. 2006..Taken together, these findings suggest that once Gab-2 is tyrosine phosphorylated its PH domain is required for the optimal stabilisation of the signalsome, enabling full activation of downstream signals...
Interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor, but not IL-4, induce tyrosine phosphorylation, activation, and association of SHPTP2 with Grb2 and phosphatidylinositol 3'-kinaseM J Welham
Biomedical Research Centre, University of British Columbia, Vancouver, Canada
J Biol Chem 269:23764-8. 1994..These results suggest that SHPTP2 may play an important role in integrating signals from the IL-3 and GM-CSF receptors to both Ras and PI 3'-kinase...
Phosphoinositide 3-kinase-dependent regulation of interleukin-3-induced proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2B L Craddock
Department of Pharmacy and Pharmacology, The University of Bath, Bath BA2 7AY, United Kingdom
J Biol Chem 276:24274-83. 2001..These results imply that the regulation of Erks by class I(A) phosphoinositide 3-kinase may contribute to IL-3-driven proliferation and that both SHP2 and Gab2 are possibly involved in this regulation...
Differential coupling of self-renewal signaling pathways in murine induced pluripotent stem cellsLuca Orlando
Centre for Regenerative Medicine, Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
PLoS ONE 7:e30234. 2012....
Phosphoinositide 3-kinases can act independently of p27Kip1 to regulate optimal IL-3-dependent cell cycle progression and proliferationBridget C Fox
Department of Pharmacy and Pharmacology, The University of Bath, Claverton Down, Bath BA2 7AY, UK
Cell Signal 17:473-87. 2005....
Molecular interactions of SHP1 and SHP2 in IL-3-signallingHelen Wheadon
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY, Bath, UK
Cell Signal 14:219-29. 2002..These studies suggest that SH2-domain interactions are important for targetting these phosphatases to their substrates...
A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3Heather K Bone
Centre for Regenerative Medicine and Department of Pharmacy and Pharmacology, University of Bath, Bath BA27AY, UK
J Cell Sci 124:1992-2000. 2011..These findings describe, for the first time, the utility of GSK-3 inhibition, in a chemically directed approach, to a method of DE generation that is robust, potentially scalable and applicable to different hESC lines...
Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domainsH Bone
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, UK
Cell Signal 12:183-94. 2000..PTB binding to IL-3R beta chains was of highest affinity, and appeared to play the primary role in binding. These findings suggest that Shc may play an important role in coordinately integrating IL-3 signalling pathways...
A novel role for P2X7 receptor signalling in the survival of mouse embryonic stem cellsBelinda A N Thompson
Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
Cell Signal 24:770-8. 2012..Together, these data demonstrate a novel role for P2X7 receptors in regulation of ES cell behaviour where they can mediate either a pro-survival or pro-death signal depending on the mode of activation...
Characterization of the phosphoinositide 3-kinase-dependent transcriptome in murine embryonic stem cells: identification of novel regulators of pluripotencyMichael P Storm
Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Bath, United Kingdom
Stem Cells 27:764-75. 2009..Further gain-of-function analyses demonstrate the importance of Zscan4c in regulation of ES cell pluripotency...
Isolation of C15: a novel antibody generated by phage display against mesenchymal stem cell-enriched fractions of adult human marrowJulie Letchford
Department of Pharmacy and Pharmacology and Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom
J Immunol Methods 308:124-37. 2006....
p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating proteinV Duronio
Biomedical Research Centre, University of British Columbia, Vancouver, Canada
Proc Natl Acad Sci U S A 89:1587-91. 1992..Attempts to demonstrate tyrosine phosphorylation of the p21ras GTPase-activating protein (GAP) were negative, suggesting that phosphorylation of GAP may not be the major mechanism for regulation of p21ras activity by tyrosine kinases...
Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal revealed by a series of bisindolylmaleimidesHeather K Bone
Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Bath, UK
Chem Biol 16:15-27. 2009..Our study clarifies the functional importance of GSK-3 in regulation of ESC self-renewal and provides tools for investigating its role further...
SHP1 and SHP2 protein-tyrosine phosphatases associate with betac after interleukin-3-induced receptor tyrosine phosphorylation. Identification of potential binding sites and substratesH Bone
School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom
J Biol Chem 272:14470-6. 1997..Binding of these protein-tyrosine phosphatases to the IL-3 receptor may regulate IL-3 signal transduction pathways, both through their catalytic activity and through the recruitment of other molecules to the receptor complex...
Three-dimensional culture systems for the expansion of pluripotent embryonic stem cellsMichael P Storm
Centre for Regenerative Medicine, Departments of Pharmacy and Pharmacology, University of Bath, Bath, UK
Biotechnol Bioeng 107:683-95. 2010..Our study highlights the importance of optimization of initial seeding parameters and provides proof-of-concept data demonstrating the utility of microcarriers and bioreactors for the expansion of hESCs...
Regulation of Nanog expression by phosphoinositide 3-kinase-dependent signaling in murine embryonic stem cellsMike P Storm
Department of Pharmacy and Pharmacology and Centre for Regenerative Medicine, The University of Bath, Bath BA2 7AY, United Kingdom
J Biol Chem 282:6265-73. 2007..Regulation of GSK-3 activity by PI3Ks appears to play a key role in this process...
Spray-dried insulin particles retain biological activity in rapid in-vitro assayN Patel
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, UK
J Pharm Pharmacol 53:1415-8. 2001..The assay may be of use as a more rapid and economic means to screen insulin formulations for inhalation and other purposes as opposed to conventional monitoring of blood glucose levels in animals...
PI3K comes of ageStephen G Ward
Nat Immunol 4:2. 2003
The PI3K inhibitor arsenal: choose your weapon!Tom Crabbe
UCB Celltech, Slough, UK
Trends Biochem Sci 32:450-6. 2007..However, challenges remain for the efforts to pharmacologically target this enzyme family in a successful manner...
