The phosphoserine-585-dependent pathway of the GM-CSF/IL-3/IL-5 receptors mediates hematopoietic cell survival through activation of NF-kappa B and induction of bcl-2 Guthridge, Mark A, Barry, Emma F, Felquer, Fernando A, McClure, Barbara J, Stomski, Frank C, Ramshaw, Hayley and Lopez, Angel F 2004, The phosphoserine-585-dependent pathway of the GM-CSF/IL-3/IL-5 receptors mediates hematopoietic cell survival through activation of NF-kappa B and induction of bcl-2, BLOOD, vol. 103, no. 3, pp. 820-827, doi: 10.1182/blood-2003-06-1999. Attached Files Name Description MIMEType Size Downloads Title The phosphoserine-585-dependent pathway of the GM-CSF/IL-3/IL-5 receptors mediates hematopoietic cell survival through activation of NF-kappa B and induction of bcl-2 Author(s) Guthridge, Mark A orcid.org/0000-0002-0536-3471 Barry, Emma F Felquer, Fernando A McClure, Barbara J Stomski, Frank C Ramshaw, Hayley Lopez, Angel F Journal name BLOOD Volume number 103 Issue number 3 Start page 820 End page 827 Total pages 8 Publisher AMER SOC HEMATOLOGY Place of publication United States Publication date 2004-02-01 ISSN 0006-4971 1528-0020 Keyword(s) Science & Technology Life Sciences & Biomedicine Hematology MULTIPLE SIGNALING PATHWAYS COMMON BETA-CHAIN FACTOR GM-CSF TYROSINE RESIDUES THROMBOPOIETIN RECEPTOR SERINE PHOSPHORYLATION DIFFERENTIATION PROLIFERATION EXPRESSION INTERACTS Summary AbstractWe have recently identified a novel mechanism of hematopoietic cell survival that involves site-specific serine phosphorylation of the common beta subunit (βc) of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors. However, the downstream components of this pathway are not known, nor is its relationship to survival signals triggered by tyrosine phosphorylation of the receptor clear. We have now found that phosphorylation of Ser585 of βc in response to GM-CSF recruited 14-3-3 and phosphatidyl inositol 3-OH kinase (PI 3-kinase) to the receptor, while phosphorylation of the neighboring Tyr577 within this “viability domain” promoted the activation of both Src homology and collagen (Shc) and Ras. These are independent processes as demonstrated by the intact reactivity of phosphospecific anti-Ser585 and anti-Tyr577 antibodies on the cytotoxic T-lymphocyte–ecotrophic retroviral receptor neomycin (CTL-EN) mutants βcTyr577Phe and βcSer585Gly, respectively. Importantly, while mutants in which either Ser585 (βcSer585Gly) or all tyrosines (βcF8) were substituted showed a defect in Akt phosphorylation, nuclear factor κB (NF-κB) activation, bcl-2 induction, and cell survival, the mutant βcTyr577Phe was defective in Shc, Ras, and extracellular signal-related kinase (ERK) activation, but supported CTL-EN cell survival in response to GM-CSF. These results demonstrate that both serine and tyrosine phosphorylation pathways play a role in hematopoietic cell survival, are initially independent of each other, and converge on NF-κB to promote bcl-2 expression. Language eng DOI 10.1182/blood-2003-06-1999 Indigenous content off Field of Research 1102 Cardiorespiratory Medicine and Haematology 1103 Clinical Sciences 1114 Paediatrics and Reproductive Medicine HERDC Research category C1 Refereed article in a scholarly journal Persistent URL http://hdl.handle.net/10536/DRO/DU:30134403 Document type: Journal Article Collections: Faculty of Science, Engineering and Built Environment School of Life and Environmental Sciences Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Fri, 31 Jan 2020, 14:40:31 EST Sat, 01 Feb 2020, 04:04:58 EST Sat, 01 Feb 2020, 05:05:47 EST Wed, 21 Oct 2020, 09:07:59 EST Wed, 21 Oct 2020, 09:09:13 EST Wed, 21 Oct 2020, 11:56:59 EST Filtered Full Citation counts:   Cited 58 times in TR Web of Science Cited 0 times in Scopus Search Google Scholar Access Statistics: 42 Abstract Views, 1 File Downloads  -  Detailed Statistics Created: Fri, 31 Jan 2020, 14:40:31 EST

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