MAP KINASE FAMILY MEMBERS ARE PHOSPHORYLATED IN MICE SKELETAL MUSCLE CELLS BY THE STEROID HORMONE 1-25(OH)2D3

CLAUDIA BUITRAGO; ANA CAROLINA RONDA; ANA RUSSO DE BOLAND; RICARDO BOLAND

BOSTON, MASSACHUSETTS, USA

Congreso; ASBMB ANNUAL MEETING AND 8TH IUBMB CONFERENCE; 2004

AMERICAN SOCIETY FOR BIOCHEMESTRY AND MOLECULAR BIOLOGY

In chick skeletal muscle cell primary cultures we previously demostrated that 1a,25(OH)2-vitamin D3 increases the phosphorylation and activity of the extracellular signal-regulated mitogen-activated protein (MAP) kinase isoforms ERK1 and ERK2, their subsequent traslocation to the nucleus and  involvement in DNA synthesis stimulation. Using the mice myoblast cell line C2C12, we observed similar results in hormone dependent-ERK 1/2 phosphorylation. Furthermore, in accordance with the role of ERK 1/2 in cell proliferation, 1a,25(OH)2-vitamin D3 induced a fast phosphorylation of the transcription factor Elk-1 in these cells. Other members of the MAP kinase superfamily were also phosphorylated by the hormone. When C2C12 cells were stimulated with 1a,25(OH)2-vitamin D3, fast (0.5 - 1 min) phosphorylation of p38 was observed. Moreover, we demostrated an increase in p38 kinase activity in response to the steroid. The immediately upstream kinases MKK3/MKK6 were also phosphorylated by the hormone suggesting their participation in p38 activation. 1a,25(OH)2-vitamin D3 was able to dephosphorylate/activate the ubiquitous  cytosolic tyrosine kinase c-Src in C2C12 cells and studies with specific inhibitors imply that Src participates in hormone induced-p38 activation. Initial experiments reveal that 1a,25(OH)2-vitamin D3 promotes the phosphorylation of c-jun N-terminal protein kinases (JNK 1/2) and the big kinase ERK5. Further investigations will establish the relative contribution of ERK 1/2, p38, JNK 1/2 and ERK 5 and their interrelationships in hormonal regulation of muscle cell proliferation and differentiation.