DAPP1 undergoes a PI 3-kinase-dependent cycle of plasma-membrane recruitment and endocytosis upon cell stimulation

Autor: S. H. Ridley, L. Stephens, Martin D. Bootman, Hediye Erdjument-Bromage, J.W. Thuring, Johan Lennartsson, Anita Grewal, Andrew B. Holmes, Ze-Yi Lim, Paul Tempst, Karen E. Anderson, Lars Rönnstrand, Peter Lipp, Gavin F. Painter, P. T. Hawkins, John Coadwell
Rok vydání: 2000
Předmět:
Endosome
Swine
Lipoproteins
Recombinant Fusion Proteins
Biology
Endocytosis
General Biochemistry
Genetics and Molecular Biology
Cell Line
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
Epidermal growth factor
Animals
Phosphatidylinositol
Phosphorylation
Transport Vesicles
Platelet-Derived Growth Factor
B-Lymphocytes
Binding Sites
Agricultural and Biological Sciences(all)
Biochemistry
Genetics and Molecular Biology(all)
Cell Membrane
Fatty Acids
Membrane Proteins
Biological Transport
Blood Proteins
Phosphoproteins
Cell biology
Pleckstrin homology domain
Enzyme Activation
chemistry
biology.protein
Tyrosine
Signal transduction
General Agricultural and Biological Sciences
Carrier Proteins
Chickens
Platelet-derived growth factor receptor
Proto-oncogene tyrosine-protein kinase Src
Signal Transduction
Zdroj: Current biology : CB. 10(22)
ISSN: 0960-9822
Popis: BACKGROUND: Phosphoinositide (PI) 3-kinase and its second messenger products, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P(2)), play important roles in signalling processes crucial for cell movement, differentiation and survival. Previously, we isolated a 32kDa PtdIns(3,4,5)P(3)-binding protein from porcine leukocytes. This protein contains an amino-terminal Src homology 2 (SH2) domain and a carboxy-terminal pleckstrin homology (PH) domain, and is identical to the recently described DAPP1 (also known as PHISH or Bam32) protein. Here, we characterised the subcellular distribution of DAPP1 in response to cell stimulation. RESULTS: When expressed transiently in porcine aortic endothelial (PAE) cells, DAPP1 translocated from the cytosol to the plasma membrane in response to platelet-derived growth factor (PDGF). This translocation was dependent on both PI 3-kinase activity and an intact DAPP1 PH domain. Following recruitment to the plasma membrane, DAPP1 entered the cell in vesicles. Similar responses were seen in DT40 chicken B cells following antibody treatment, and Rat-1 fibroblasts following epidermal growth factor (EGF) or PDGF treatment. Colocalisation studies in PAE cells suggested entry of DAPP1 by endocytosis in a population of early endosomes containing internalised PDGF-beta receptors. DAPP1 also underwent PI 3-kinase-dependent phosphorylation on Tyr139 in response to PDGF stimulation, and this event was involved in the vesicular response. CONCLUSIONS: This is the first report of plasma-membrane recruitment and endocytosis of a PI 3-kinase effector protein in response to cell stimulation. The results suggest a novel role for DAPP1 in endosomal trafficking or sorting.
Databáze: OpenAIRE
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