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Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin‐induced cell proliferation and Stat5 activation.
Author(s) -
Damen J. E.,
Wakao H.,
Miyajima A.,
Krosl J.,
Humphries R. K.,
Cutler R. L.,
Krystal G.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb00243.x
Subject(s) - biology , erythropoietin , erythropoietin receptor , stat5 , tyrosine , receptor , cell growth , receptor tyrosine kinase , tyrosine kinase , socs2 , microbiology and biotechnology , cancer research , signal transduction , endocrinology , medicine , biochemistry , gene , suppressor
While previous studies with truncated erythropoietin receptors (EpRs) have suggested that the tyrosine phosphorylation of the EpR does not play a role in Ep‐induced proliferation, we have found, using a more subtle, full length EpR mutant, designated Null, in which all eight of the intracellular tyrosines have been substituted with phenylalanine residues, that Null cells require substantially more Ep than wild‐type cells in order to proliferate as efficiently. A comparison of Ep‐induced proliferation with Ep‐induced tyrosine phosphorylation patterns, using wild‐type and Null EpR‐expressing cells, revealed that Stat5 tyrosine phosphorylation and activation correlated directly with proliferation. Moreover, studies with a Y343F EpR point mutant and various EpR deletion mutants revealed that both Ep‐induced proliferation and Stat5 activation were mediated primarily through Y343, but that other tyrosines within the EpR could activate Stat5 in its absence.