Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response. Mol Cell Biol 1996 Apr;16(4):1622-31
Date
04/01/1996Pubmed ID
8657137Pubmed Central ID
PMC231148DOI
10.1128/mcb.16.4.1622Scopus ID
2-s2.0-0029866781 238 CitationsAbstract
The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a membrane-distal region that is dispensable for mitogenesis but is required for the recruitment and tyrosine phosphorylation of a variety of signaling proteins. The membrane-proximal region of 96 amino acids is necessary and sufficient for mitogenesis as well as Jak2 activation, induction of c-fos, c-myc, cis, the T-cell receptor gamma locus (TCR-gamma), and c-pim-1. The studies presented here demonstrate that this region is also necessary and sufficient for the activation of Stat5A and Stat5B. The membrane-proximal domain contains a single tyrosine, Y-343, which when mutated eliminates the ability of the receptor to couple Epo binding to the activation of Stat5. Furthermore, peptide competitions demonstrate that this site, when phosphorylated, can disrupt Stat5 DNA binding activity, consistent with a role of Y-343 as a site of recruitment to the receptor. Cells expressing the truncated, Y343F mutant (a mutant with a Y-to-F alteration at position 343) proliferate in response to Epo in a manner comparable to that of the controls. However, in these cells, Epo stimulation does not induce the appearance of transcripts for cis, TCR-gamma, or c-fos, suggesting a role for Stat5 in their regulation.
Author List
Quelle FW, Wang D, Nosaka T, Thierfelder WE, Stravopodis D, Weinstein Y, Ihle JNAuthor
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Cell Division
Cell Line
DNA-Binding Proteins
Enzyme Activation
Erythropoietin
Humans
Janus Kinase 2
Milk Proteins
Molecular Sequence Data
Mutation
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Receptors, Antigen, T-Cell, gamma-delta
Receptors, Erythropoietin
STAT5 Transcription Factor
Trans-Activators
Tumor Suppressor Proteins
Tyrosine
