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

  

Authors:	Anderson, K. E.; Lipp, P.; Bootman, M.; Ridley, S. H.; Coadwell, J.; Rönnstrand, L.; Lennartsson, J.; Holmes, A. B.; Painter, G. F.; Thuring, J.; Lim, Z. Y.; Erdjument-Bromage, H.; Grewal, V.; Tempst, P.; Stephens, L. R.; Hawkins, P. T.
Article Title:	DAPP1 undergoes a PI 3-kinase-dependent cycle of plasma-membrane recruitment and endocytosis upon cell stimulation
Abstract:	Background: Phosphoinositide (PI) 3-kinase and its second messenger products, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), play important roles in signalling processes crucial for cell movement, differentiation and survival. Previously, we isolated a 32 kDa PtdIns(3,4,5)P3-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-β 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.
Keywords:	signal transduction; platelet derived growth factor; carrier protein; genetics; blood proteins; animal; cytology; metabolism; animals; cell line; membrane proteins; enzyme activation; drug effect; tyrosine; phosphorylation; phosphatidylinositol 3 kinase; physiology; b lymphocyte; animalia; b-lymphocytes; hybrid protein; recombinant fusion proteins; carrier proteins; membrane protein; cell membrane; 1-phosphatidylinositol 3-kinase; platelet-derived growth factor; phosphoproteins; binding site; binding sites; fatty acids; endocytosis; fatty acid; phosphoprotein; swine; biological transport; suidae; plasma protein; chickens; transport at the cellular level; chicken; lipoproteins; transport vesicle; transport vesicles; lipoprotein; article; sus scrofa; gallus gallus; platelet protein p47
Journal Title:	Current Biology
Volume:	10
Issue:	22
ISSN:	0960-9822
Publisher:	Cell Press
Date Published:	2000-11-14
Start Page:	1403
End Page:	1412
Language:	English
DOI:	10.1016/s0960-9822(00)00794-6
PUBMED:	11102801
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-17844405295&partnerID=40&md5=0d73f8e5f4d800eb40c987c44630920d
Notes:	Export Date: 18 November 2015 -- Source: Scopus

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