DAPP1 undergoes a PI 3-kinase-dependent cycle of plasma-membrane recruitment and endocytosis upon cell stimulation.
| Autor: | Anderson KE; Laboratory of Molecular Signalling, The Babraham Institute, Babraham, CB2 4AT, Cambridge, UK. karen.anderson@bbsrc.ac.uk, Lipp P, Bootman M, Ridley SH, Coadwell J, Rönnstrand L, Lennartsson J, Holmes AB, Painter GF, Thuring J, Lim Z, Erdjument-Bromage H, Grewal A, Tempst P, Stephens LR, Hawkins PT |
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| Jazyk: | angličtina |
| Zdroj: | Current biology : CB [Curr Biol] 2000 Nov 16; Vol. 10 (22), pp. 1403-12. |
| DOI: | 10.1016/s0960-9822(00)00794-6 |
| Abstrakt: | 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: | MEDLINE |
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