Membrane origin for a signal eliciting a program of cell differentiation

Evidence is presented to indicate that the retiNOic acid (RA)-induced program of myeloid differentiation and growth arrest by HL-60 human promyelocytic leukemia cells was initiated by a signal originating at the cell membrane. Free RA and RA covalently immobilized on a solid substrate elicited similar kinetics of differentiation and G1/0-specific growth arrest. No evidence of cell-induced RA detachment from the solid substrate was found. The data explain why HL-60 cells which are deficient in cellular RA-binding protein (CRABP) nevertheless respond to RA.