Involvement of the p38 mitogen‐activated protein kinase pathway in tissue inhibitor of metalloproteinases‐1‐induced erythroid differentiation

We examined the role of the mitogen‐activated protein (MAP) kinase pathway in tissue inhibitor of metalloproteinases‐1 (TIMP‐1)‐mediated cellular effects in a human erythroleukemic cell line UT‐7. We show that TIMP‐1 induced both UT‐7 cell erythroid differentiation and proliferation and tyrosine phosphorylation of many intracellular proteins. Using a panel of phosphospecific antibodies, we also demonstrate that phosphorylation of the p38 and c‐Jun N‐terminal kinases is increased by TIMP‐1 whereas phosphorylation of extracellular signal‐regulated kinase 1/2 is not induced. Moreover, inhibition of the p38 activity by SB203580 significantly reduces erythroid differentiation induced by TIMP‐1, suggesting that the p38 MAP kinase pathway is involved in TIMP‐1‐induced erythroid differentiation.