The role of serine/threonine phosphorylation in hematopoietic cytokine receptor signal transduction.

The hematopoietic cytokine receptors rapidly activate tyrosine phosphorylation after ligand engagement. In addition, however, serine/threonine phosphorylation of important effector molecules also icreases. Interleukins 2-5 and granulocyte-macrophage colony stimulating factor all activate protein kinase C. This results in serine/threonine phosphorylation of such important regulatory molecules as Raf-1 kinase, myristoylated alanine-rich C kinase substrate, and SOS. These phosphorylated effector molecules are regulators of important genes related to cell survival and proliferation. In addition, as yet uncharacterized serine/threonine kinases associate directly with the hematopoietic receptor subunits themselves. These kinases may contribute to the phosphorylation of the STAT family of transcription factors that is important in regulating cytokine-specific gene inductions. Thus, it is time to begin integrating serine/threonine kinases into the postulated signaling pathways activated by hematopoietic cytokine receptors.