A non-canonical Grb2-PLC-gamma1-Sos cascade triggered by lipovitellin 1, an apolipoprotein B homologue.
The injection of the Grb2 adapter in Xenopus oocytes promotes G2/M transition without stimulation from a receptor only the first day after the oocytes removal from the ovaries. This cell cycle reinitiation is Ras-dependent and requires the SH2 and SH3 domains of Grb2. The SH2 domain of Grb2 binds the tyrosine phosphorylated lipovitellin1, a homologue of the human apolipoprotein B. The N-SH3 domain of Grb2 is linked to a proline-rich sequence of the C2 domain of PLC-gamma1, PLC-gamma1 itself is linked, through its SH3 domain, to the C-terminal proline-rich region of Sos. When Grb2-PLC-gamma1-Sos is associated, PLC-gamma1 is not phosphorylated on Y783 but shows a phospholipase activity. Inhibition of lipovitellin 1 or PLC-gamma1 avoids Grb2-induced cell cycle reinitiation. Therefore, the Grb2-lipovitellin 1 association is the starting point of a novel signaling pathway, where PLC-gamma1 binds Grb2 and recruits Sos.
Browaeys-Poly
Edith
E
Laboratoire de Régulation des Signaux de Division, EA 4020, IFR 147, Bât. SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France. edith.browaeys@univ-lille1.fr
Broutin
Isabelle
I
Antoine
Anne-Frédérique
AF
Marin
Matthieu
M
Lescuyer
Arlette
A
Vilain
Jean Pierre
JP
Ducruix
Arnaud
A
Cailliau
Katia
K
D000818:Animals; D002453:Cell Cycle; D004527:Egg Proteins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D051380:GRB2 Adaptor Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009865:Oocytes; D051966:Phospholipase C gamma / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D020664:Son of Sevenless Proteins / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis; D018631:ras Proteins / Q000378:metabolism; D018909:src Homology Domains
D004527:Egg Proteins; D051380:GRB2 Adaptor Protein; D046912:Multiprotein Complexes; D020664:Son of Sevenless Proteins; D029867:Xenopus Proteins; D014443:Tyrosine; C001549:lipovitellin; D051966:Phospholipase C gamma; D018631:ras Proteins