GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR STIMULATES BOTH ASSOCIATION AND ACTIVATION OF PHOSPHOINOSITIDE 3OH-KINASE AND SRC-RELATED TYROSINE KINASE(S) IN HUMAN MYELOID DERIVED CELLS

The signalling pathways used by the GM-CSF receptor are currently unkn own. Here we show that in human myeloid derived cells GM-CSF can stimu late; (i) the accumulation of PtdIns(3,4,5)P3; (ii) increases in p53/p 56lyn and p62c-yes directed protein tyrosine kinase activities in anti -lyn and anti-c-yes antibody directed immunoprecipitates, respectively and; (iii) increases in phosphoinositide 3OH-kinase activity in anti- phosphotyrosine, anti-p53/p56lyn and anti-p62c-yes antibody directed i mmunoprecipitates. These results suggest that GM-CSF can stimulate for mation of protein tyrosine kinase co-ordinated signalling complexes, t hat contain p53/p56lyn, p62c-yes and an activated PtdInsP2 directed ph osphoinositide 3OH-kinase, which can drive the accumulation of the put ative second-messenger PtdIns(3,4,5)P3.