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.
Mufson
R A
RA
Immunology Department, Jerome Holland Laboratory, American Red Cross, Rockville, Maryland 19855, USA.
D000818:Animals; D006413:Hematopoietic System / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D018121:Receptors, Cytokine / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013912:Threonine / Q000378:metabolism*
D018121:Receptors, Cytokine; D013912:Threonine; D012694:Serine; D017346:Protein Serine-Threonine Kinases