C-CAM-mediated adhesion leads to an outside-in dephosphorylation signal.
The rat cell-cell adhesion molecule C-CAM, a member of the carcinoembryonic antigen family, was shown to be expressed in various isoforms, differing in the length of the cytoplasmic domain. The long isoform C-CAML inhibits the growth of different malignant cells. Several studies suggest that it is involved in the mechanism of signal transduction. So far no direct correlation between C-CAM function and C-CAM phosphorylation has been reported. In the present study we addressed the question of whether C-CAM-mediated adhesion is accompanied by changes in phosphorylation of the cytoplasmic domain of C-CAM. It was demonstrated that C-CAML is constitutively phosphorylated in adherent growing cells as well as in cells growing in suspension. In contrast, C-CAML-mediated cell aggregation is accompanied by a 40% reduction in C-CAML phosphorylation compared with nonaggregated cells. The same dephosphorylation was achieved by antibody-induced clustering of C-CAML in the plasma membrane. Phosphorylation and dephosphorylation indicate a C-CAM-mediated outside-in signalling induced by cell-cell adhesion.
Lucka
L
L
Institut für Molekularbiologie und Biochemie, Universitätsklinikum Benjamin Franklin, Freie Universität Berline, Germany. lucka@zedat.fu-berlin.de
Budt
M
M
Cichocka
I
I
Danker
K
K
Horstkorte
R
R
Reutter
W
W
D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002462:Cell Membrane; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D015398:Signal Transduction
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006023:Glycoproteins