Granulocyte-macrophage colony-stimulating factor, interleukin-3, and steel factor induce rapid tyrosine phosphorylation of p42 and p44 MAP kinase.

摘要: Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-3 (IL-3), and Steel Factor (SF) induce proliferation of hematopoietic cells through binding to specific, high-affinity, cell surface receptors. However, little is known about postreceptor signal transduction pathways. In previous studies, we noted that each these three factors could independently support the human MO7 line, also induced a rapid increase in protein-tyrosyl phosphorylation. Although proteins phosphorylated on tyrosine by GM-CSF IL-3 are similar or identical cells, many after SF different. two proteins, p42 p44, were prominently response all factors. tyrosyl phosphorylation p44 was transient, peaking at 5 15 minutes. contrast other which factors, temperature-dependent, occurring 37 degrees C, but not 4 C. We identified protein as Mitogen-Activated Protein Kinase (p42mapk, ERK-2) p42mapk-related using monospecific antisera MAP kinase. GM-CSF, IL-3, found kinase activity when assayed vitro myelin basic (MBP) substrate. Remarkably, GM-CSF-induced even nonproliferative (neutrophils) respond this CSF, most following stimulation cells. These results implicate p42mapk important transducing molecules myeloid it likely kinases play role part sequential "kinase cascade" linking growth receptors mitogenesis cellular responses.