hCEACAM1-4L downregulates hDAF-associated signalling after being recognized by the Dr adhesin of diffusely adhering Escherichia coli.
Human decay accelerating factor (hDAF, CD55) and members of the carcinoembryonic-antigen-related cell-adhesion molecules (hCEACAMs) family are recognized as receptors by Gram-negative, diffusely adhering Escherichia coli (DAEC) strains expressing Afa/Dr adhesins. We report here that hCEACAM1-4L has a key function in downregulating the protein tyrosine Src kinase associated with hDAF signalling. After infecting HeLa epithelial cells stably transfected with hCEACAM1-4L cDNA with Dr adhesin-positive E. coli, the amount of the pTyr(416)-active form of the Src protein decreased, whereas that of the pTyr(527)-inactive form of Src protein did not increase. This downregulation of the Src protein implies that part of the hCEACAM1-4L protein had been translocated into lipid rafts, the protein was phosphorylated at Tyr residues in the cytoplasmic domain, and it was physically associated with the protein tyrosine phosphatase, SHP-2. Finally, we found that the hCEACAM1-4L-associated SHP-2 was not phosphorylated and lacked phosphatase activity, suggesting that the downregulation of Src protein associated with hDAF signalling results from the absence of dephosphorylation of the pTyr(527)-inactive form necessary for Src kinase activation.
Rougeaux
Clémence
C
INSERM, UMR756 Signalisation et Physiopathologie des Cellules Epithéliales, Châtenay-Malabry, France, and Université Paris-Sud XI, Faculté de Pharmacie, Châtenay-Malabry, France.
Berger
Cédric N
CN
Servin
Alain L
AL
D018830:Adhesins, Escherichia coli / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015536:Down-Regulation; D004926:Escherichia coli / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D018830:Adhesins, Escherichia coli; D015703:Antigens, CD; D018958:CD55 Antigens; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C465564:Dr adhesin, E coli; D019061:src-Family Kinases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11