INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Targets of SHP2 tyrosine phosphatase regulated by cAMP in MA-10 Leydig cells
Autor/es:
MALOBERTI, P.; MUÑOZ, M.; NEUMAN, I.; PODESTA, E.J.; CORNEJO MACIEL, F.
Lugar:
Rosario, Santa Fe
Reunión:
Congreso; L Reunión Anual Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2014
Institución organizadora:
Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)
Resumen:
SHP2 is a ubiquitously expressed non-transmembrane protein tyrosine phosphatase, that serves multiple hormone receptors. In steroidogenic tissues, it is involved in the cAMP-dependent and independent acute stimulation of steroid production. However, the targets that relate Ser/Tre phosphorylation with Tyr dephosphorylation are poorly known. Thus, our aim was to analyze the targets of SHP2 in protein modifications triggered by cAMP. For that purpose, we performed a reverse phase protein array (RPPA), a high throughput antibody-based technique developed for functional proteomics studies. MA-10 Leydig cells were transfected with or without specific SHP2 shRNA and incubated 15 min with or without 0.5 mM cAMP, prior to the RPPA. The results indicate that SHP2 up or down regulates cAMP action depending on the target. SHP2 upregulates the changes triggered by cAMP on cMyc, G6PDH, Histone H3, Notch1, eIF4G, CDK1, N-Cadherin levels, while it inhibits cAMP action on GSK3 and AKT phosphorylation. The activation of ERK1/2 is one of the widely described targets of SHP2 in other systems, as well as of cAMP action in steroidogenic cells. However, in the later, we found that cAMP increases ERK1/2 phosphorylation in a SHP2 independent fashion. The results suggest that the participation of SHP2 on cAMP action is dependent on the intracellular location of cAMP/PKA, SHP2 and their respective targets.