Activation of mitogen-activated protein kinase cascade through erythropoietin receptor.
Erythropoietin is a cytokine which specifically regulates differentiation and proliferation of erythroid progenitor cells. We show here that binding of erythropoietin to its receptor induced activation of protein tyrosine kinases including Jak2, and of Ras, Raf-1, mitogen-activated protein (MAP) kinase kinase and MAP kinases (ERK1 and ERK2). Taken together with other observations, erythropoietin receptor-mediated signal activates MAP kinase cascade, which is the common signaling pathway activated by other cytokines and growth factor receptors with tyrosine kinase activity.
Todokoro
K
K
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Sugiyama
M
M
Nishida
E
E
Nakaya
K
K
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D008954:Models, Biological; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection; D014168:Transferrin / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D010750:Phosphoproteins; D017467:Receptors, Erythropoietin; D015375:Receptors, Interleukin-2; D014168:Transferrin; D004921:Erythropoietin; D019000:Phosphotyrosine; D014443:Tyrosine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases