N-terminal c-Fos tyrosine phosphorylation regulates c-Fos/ER association and c-Fos-dependent phospholipid synthesis activation

GABRIEL ORLANDO FERRERO; MAXIMILIANO MOISES PORTAL; BEATRIZ LEONOR CAPUTTO

Rosario, Santa Fe, Argentina

Congreso; Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2006

Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

c-Fos, a component of the AP-1 family of transcription factors, is expressed at very low levels in resting cells. However, its expression is rapidly up regulated in cells undergoing G0 to S phase transition leading to AP-1-dependent gene transcription responses. In addition, cytoplasmic c-Fos associates to the endoplasmic reticulum (ER) membranes and activates phospholipid synthesis during cell growth and differentiation. Herein, it is shown that in T98G cells, c-Fos/ER association and consequently phospholipid synthesis activation is regulated by the phosphorylated state of c-Fos tyrosine residues. The small amount of c-Fos present in quiescent T98G cells is tyrosine-phosphorylated and not ER-membrane bound. In growing cells, itis dephosphorylated, associated to ER membranes and promotes phospholipid synthesis activation. Impairing tyr-dephosphorylation abrogates phospholipid synthesis activation and reduces proliferation rates to those of quiescent cells. Substitution of tyrosine residues 10, 30, 106 and 337 evidence tyr 10 and 30 as relevant for this regulatory phenomenon. It is concluded that phosphorylation of tyrosine residues 10 and 30 of c-Fos regulate the rate of synthesis of phospholipids by regulating c-Fos/ER association. At present, we are looking for the tirosine-kinase and tirosine-phosphatase of c-Fos, as a possible target to control cell growth.