The extended box 2 subdomain of erythropoietin receptor is nonessential for Jak2 activation yet critical for efficient mitogenesis in FDC-ER cells

Tong-Chuan He; Ning Jiang; Hongming Zhuang; Dawn E Quelle; Don M Wojchowski

doi:10.1016/S0021-9258(17)32302-5

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The extended box 2 subdomain of erythropoietin receptor is nonessential for Jak2 activation yet critical for efficient mitogenesis in FDC-ER cells

Journal article

Open access

Peer reviewed

The extended box 2 subdomain of erythropoietin receptor is nonessential for Jak2 activation yet critical for efficient mitogenesis in FDC-ER cells

Tong-Chuan He, Ning Jiang, Hongming Zhuang, Dawn E Quelle and Don M Wojchowski

The Journal of biological chemistry, Vol.269(28), pp.18291-18294

07/15/1994

DOI: 10.1016/S0021-9258(17)32302-5

PMID: 8034573

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Abstract

The development of erythroid progenitor cells depends upon exposure to the glycoprotein hormone, erythropoietin (EPO). Binding of EPO to its transmembrane receptor leads to the rapid tyrosine phosphorylation of several cellular targets including Shc, Raf-1, Gap120, the cloned EPO receptor (EPOR), pp100/97, and a M(r) 130,000 EPO-activated receptor-associated Janus protein tyrosine kinase, Jak2. A membrane-proximal cytosolic region of the EPOR recently has been shown to be essential for the activation of Jak2 and sufficient for EPO-induced mitogenesis. This cytosolic region includes 8-12 amino acid box 1 and box 2 subdomains, which are conserved in certain class I receptors as well as a more distal 10-40 amino acid subdomain (extended box 2 subdomain, ExBx2), which likewise is implicated in mitogenic signaling. Through the expression of EPOR carboxyl-terminal truncation mutants in FDC-P1 cells, we presently show that an EPOR form truncated within the ExBx2 domain efficiently activates Jak2, yet is deficient in mitogenesis. Efficient expression of this mutant receptor at the cell surface and its ability to activate Jak2 indicate that poor mitogenic activity does not result from aberrant transport or folding. Rather, failure of this mutant to support proliferation above nominal rates underlines an apparent role for the EPOR ExBx2 subdomain in the activation of a distinct primary mitogenic effector.

Mutagenesis

Transfection

Erythropoietin - pharmacology

Recombinant Proteins - metabolism

Amino Acid Sequence

Cell Line

Protein-Tyrosine Kinases - metabolism

Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology

Molecular Sequence Data

Recombinant Proteins - chemistry

Interleukin-3 - pharmacology

Cell Division - drug effects

Janus Kinase 2

Animals

Receptors, Erythropoietin - chemistry

Cloning, Molecular

Cell Membrane - metabolism

Mice

Proto-Oncogene Proteins

Enzyme Activation

Erythropoietin - metabolism

Kinetics

Receptors, Erythropoietin - metabolism

Binding Sites

Details

Title: Subtitle: The extended box 2 subdomain of erythropoietin receptor is nonessential for Jak2 activation yet critical for efficient mitogenesis in FDC-ER cells
Creators: Tong-Chuan He - Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802
Ning Jiang
Hongming Zhuang
Dawn E Quelle
Don M Wojchowski
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.269(28), pp.18291-18294
DOI: 10.1016/S0021-9258(17)32302-5
PMID: 8034573
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: K04HL03042 / NHLBI NIH HHS R01HL44491 / NHLBI NIH HHS
Language: English
Date published: 07/15/1994
Academic Unit: Pathology; Neuroscience and Pharmacology
Record Identifier: 9984040554102771

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