Adherence of human erythroleukemia cells inhibits proliferation without inducing differentiation

To investigate the effect of extracellular matrix molecules in the megakary ocytic lineage, we studied the role of integrin engagement in the prolifera tion and differentiation of human erythroleukemia (HEL) cells. HEL cells gr ew in suspension, but their adherence depended upon the presence of matrix proteins or protein kinase C signaling. Adherence by itself did not trigger commitment of these cells but accelerated phorbol 12-myristate 13-acetate- induced differentiation, HEL cells adhered to fibronectin mainly through al pha 5 beta 1, and this receptor acted synergetically with alpha 4 beta 1, I ntegrin engagement induced cell growth arrest through mitogen-activated pro tein kinase inactivation. Such down-regulation of the mitogen-activated pro tein kinase pathway by integrin engagement was suggested as a megakaryocyti c-platelet lineage specificity. This signaling was not restricted to a pecu liar integrin but was proposed as a general mechanism in these cells.