The G-protein-coupled CCK2 receptor associates with phospholipase Cgamma1.
In ElasCCK2 transgenic mice expressing cholecystokinin (CCK2) receptor in acinar cells, pancreatic phenotypic alterations and preneoplastic lesions are observed. We determined whether activation of phospholipase C gamma1 (PLCgamma1), known to contribute to the tumorigenesis pathophysiology, could take place as a new signaling pathway induced by the CCK2 receptor. Overexpression and activation of the PLCgamma1 in response to gastrin was observed in acinar cells. The possibility that the C-terminal tyrosine 438 of the CCK2 receptor associates with the SH2 domains of PLCgamma1 was examined. A specific interaction was demonstrated using surface plasmon resonance, confirmed in a cellular system and by molecular modeling.
Arnould
Marika
M
INSERM U531, Institut Louis Bugnard, IFR31, CHU Rangueil, Bât L3, Toulouse, France.
Tassa
Amina
A
Ferrand
Audrey
A
Archer
Elodie
E
Estève
Jean-Pierre
JP
Pénalba
Virginie
V
Portolan
Ghislaine
G
Escherich
Achim
A
Moroder
Luis
L
Fourmy
Daniel
D
Seva
Catherine
C
Dufresne
Marlène
M
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D007150:Immunohistochemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma; D011485:Protein Binding; D043887:Receptor, Cholecystokinin B / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D043887:Receptor, Cholecystokinin B; D014443:Tyrosine; D010738:Type C Phospholipases; D051966:Phospholipase C gamma