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Colocalization of the VEGF‐R2 and the common IL‐3/GM‐CSF receptor beta chain to lipid rafts leads to enhanced p38 activation
Author(s) -
Saulle Ernestina,
Riccioni Roberta,
Coppola Simona,
Parolini Isabella,
Diverio Daniela,
Riti Viviana,
Mariani Gualtiero,
Laufer Stefan,
Sargiacomo Massimo,
Testa Ugo
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07627.x
Subject(s) - lipid raft , receptor , kinase insert domain receptor , vascular endothelial growth factor , endocrinology , microbiology and biotechnology , phosphorylation , medicine , granulocyte macrophage colony stimulating factor receptor , biology , cancer research , signal transduction , vascular endothelial growth factor a , chemistry , macrophage colony stimulating factor , macrophage , biochemistry , vegf receptors , in vitro
Summary Previous studies suggested an important role for vascular endothelial growth factor (VEGF) and its receptors in postnatal haemopoiesis. However, it is unclear how VEGF receptor (VEGFR) signalling could interact with that issued from the activation of haematopoietic growth factor receptors. To elucidate this point we explored VEGF‐R2 and granulocyte‐macrophage colony‐stimulating factor receptor (GM‐CSFR) membrane localization and cell signalling in TF1‐KDR cells (TF1 leukaemic cells that overexpress VEGF‐R2/KDR). Activation of either GM‐CSFR or VEGF‐R2 was shown to determine the migration of both receptor elements (VEGF‐R2 and the common β‐chain of the GM‐CSFR) to lipid rafts. The study of receptor phosphorylation showed that GM‐CSF induced the phosphorylation of its own receptor and the transphosphorylation of VEGF‐R2; on the other hand, VEGF triggered the phosphorylation of its receptor and transphosphorylated the β‐chain of the GM‐CSFR. Co‐stimulation of TF1‐KDR cells with both GM‐CSF and VEGF‐A resulted in massive migration of both the common GM‐CSFR β‐chain and VEGF‐R2 to lipid rafts and sustained p38 mitogen‐activated protein kinase activation. Disruption of lipid rafts inhibited the capacity of both GM‐CSF and VEGF‐A to activate p38. Experiments with specific p38 inhibitors showed that p38 activation was required to sustain the VEGF‐ and GM‐CSF‐dependent proliferation of TF1‐KDR and the survival of primary acute myeloid leukaemia blasts.