C-crk And C3g Role In The Process Of Cell Differentiation Of 3t3-l1 Adipocytes

Differentiation of 3T3-L1 preadipocytes into adipocytes is induced by a combination of inducers, including a glucocorticoid, an agent that elevates cellular cAMP, and a ligand of the insulin-like growth factor-1 receptor. Vanadate, a potent PTPase inhibitor, locks adipocyte differentiation at an early stage in the program and leds to the accumulation of p-c-CrkII, a phosphotyrosyl protein that is a substrate for PTPase HA2. Transfection of 3T3-L1 preadipocytes with a c-CrkII antisense RNA expression vector markedly reduced c-CrkII levels and prevented differentiation into adipocytes. Studies with C3G, a protein that binds to the SH3 domain in c-CrkII, showed that binding of c-CrkII with C3G correlated to the differentiation and phosphorylation of c-CrkII rendered the SH3 domain inaccessible to C3G. Taken together, these findings indicate that locking c-CrkII in the phosphorylated state with vanadate prevents its participation in the signaling system that initiates adipocyte differentiation.