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 effe cts in a human erythroleukemic cell line UT-7, We show that TIMP-1 induced both UT-7 cell erythroid differentiation and proliferation and tyrosine pho sphorylation of many intracellular proteins. Using a panel of phosphospecif ic antibodies, we also demonstrate that phosphorylation of the p38 and c-Ju n N-terminal kinases is increased by TIMP-1 whereas phosphorylation of extr acellular signal-regulated kinase 1/2 is not induced. Moreover, inhibition of the p38 activity by SB203580 significantly reduces erythroid differentia tion induced by TIMP-1, suggesting that the p38 MAP kinase pathway is invol ved in TIMP-1-induced erythroid differentiation. (C) 2000 Federation of Eur opean Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.