" 17B-Estradiol Dependent- MAPKs Activation is Mediated by PKC and c-Src in Muscle Cells¡¨.

RONDA A C; BUITRAGO C; BOLAND R

Honolulu, Hawaii, USA

Congreso; 29th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR); 2007

The classical mechanism of action of 17b-estradiol (E2) involves its binding to the intracellular estrogen receptors (ER) a or b. These ligand-activated receptors stimulate mRNA synthesis and de-novo protein expression, for hours to days. Additionally, E2 is also known to exert rapid non-genomic effects on target tissues. Some of these effects involve activation of intracellular signalling pathways. We have previously shown in C2C12 skeletal muscle cells that 10-8M E2 stimulates ERK1/2 and p38 MAPK at 15 min and that the hormone promotes phosporylation of CREB and Elk-1 transcription factors in an ERK1/2 and p38-dependent manner. In the present work, we demonstrate that E2 activates c-Src in C2C12 cells within the same time interval as ERK1/2 and p38 MAPK phosphorylation. E2-induced ERK1/2 and p38 activation was abolished by the c-Src specific inhibitor PP2, involving c-Src in hormone stimulation of MAPKs. Treatments of the muscle cells with the specific PKC inhibitor Ro318220 demonstrated that activation of ERK 1/2 and p38 in response to the estrogen is also mediated by PKC. Moreover, E2 modulates Src activation in a PKC-dependent manner, possibly through a Src protein tyrosine phosphatase. The data altogether suggest that the steroid hormone 17b-estradiol triggers upstream at PKC/Src the signalling MAPK cascades leading then to phosphorylation of CREB and Elk-1 transcription factors in the C2C12 skeletal muscle line.