Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response

Frederick W Quelle; Demin Wang; Tetsuya Nosaka; William E Thierfelder; D Stravopodis; Y Weinstein; James N Ihle

doi:10.1128/MCB.16.4.1622

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Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response

Journal article

Peer reviewed

Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response

Frederick W Quelle, Demin Wang, Tetsuya Nosaka, William E Thierfelder, D Stravopodis, Y Weinstein and James N Ihle

Molecular and cellular biology, Vol.16(4), pp.1622-1631

04/1996

DOI: 10.1128/MCB.16.4.1622

PMCID: PMC231148

PMID: 8657137

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Abstract

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.

Mutation

Erythropoietin - pharmacology

Protein-Tyrosine Kinases - metabolism

Humans

Molecular Sequence Data

Receptors, Antigen, T-Cell, gamma-delta - genetics

Receptors, Antigen, T-Cell, gamma-delta - drug effects

Receptors, Erythropoietin - genetics

DNA-Binding Proteins - metabolism

Janus Kinase 2

Protein-Tyrosine Kinases - genetics

Milk Proteins

Trans-Activators - genetics

Receptors, Erythropoietin - drug effects

Proto-Oncogene Proteins

Cell Division - genetics

Amino Acid Sequence

Cell Line

Receptors, Antigen, T-Cell, gamma-delta - metabolism

DNA-Binding Proteins - genetics

Cell Division - drug effects

Tyrosine - metabolism

Animals

STAT5 Transcription Factor

Trans-Activators - metabolism

Enzyme Activation

Receptors, Erythropoietin - metabolism

Tumor Suppressor Proteins

Details

Title: Subtitle: Erythropoietin induces activation of Stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response
Creators: Frederick W Quelle - Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
Demin Wang
Tetsuya Nosaka
William E Thierfelder
D Stravopodis
Y Weinstein
James N Ihle
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.16(4), pp.1622-1631
DOI: 10.1128/MCB.16.4.1622
PMID: 8657137
PMCID: PMC231148
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Publisher: United States
Grant note: P01 HL53749 / NHLBI NIH HHS P30 CA21765 / NCI NIH HHS
Language: English
Date published: 04/1996
Academic Unit: Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040551102771

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