JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin

@article{Witthuhn1993JAK2AW,
  title={JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin},
  author={Bruce A. Witthuhn and Frederick W. Quelle and Olli O. Silvennoinen and Taolin Yi and Bo Tang and Osamu Miura and James N. Ihle},
  journal={Cell},
  year={1993},
  volume={74},
  pages={227-236}
}
Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo.
TLDR
The results further support the hypothesis that, on Epo stimulation, JAK2 associates with the membrane-proximal cytoplasmic region of the EpoR to be activated and induces tyrosine phosphorylation of cellular substrates, including theEpoR, to transduce a growth signal.
Physical and Functional Interaction between p72 syk and Erythropoietin Receptor*
TLDR
Phosphorylation of EpoR on tyrosine residues may mediate Syk binding to the receptor through interaction between the two SH2 domains of Syk and tyrosines of the receptor.
Hematopoietic cell phosphatase associates with erythropoietin (Epo) receptor after Epo-induced receptor tyrosine phosphorylation: identification of potential binding sites.
TLDR
HCP binds the tyrosine phosphorylated Epo receptor through the amino-terminal src-homology 2 (SH2) domain of HCP, which supports the concept that, after Epo stimulation, phosphorylation of EpoR provides a docking site for HCP in the receptor complex.
Association of JAK2 and STAT5 with Erythropoietin Receptors
TLDR
It is found that phosphorylation of either serine or tyrosine residues of the EPOR can enhance the association of the receptor with JAK2, possibly increasing the sensitivity to EPO.
Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors.
TLDR
A novel mechanism specifically involved in the expansion of erythroblasts involving RON as a downstream target of the EpoR is elucidated, which was sufficient to replace EPO in progenitor expansion but not in differentiation.
Protein Kinase C α Controls Erythropoietin Receptor Signaling*
TLDR
The data suggest that PKC controls EpoR signaling instead of being a downstream effector, and PKC and phosphoinositol 3-kinase may act in concert to regulate association of theEpoR complex such that it is responsive to ligand stimulation.
Tyrosine phosphorylation of the erythropoietin receptor: role for differentiation and mitogenic signal transduction.
TLDR
The mutated receptors all induced the tyrosine phosphorylation of several cellular proteins after Epo stimulation, suggesting that phosphorylated tyrosines of the receptor could have a role in the recruitment either of a tyrosin kinase or of tyrosINE kinase substrate proteins.
Erythropoietin Receptors Associate with a Ubiquitin Ligase, p33RUL, and Require Its Activity for Erythropoietin-induced Proliferation*
TLDR
It is shown that RUL is phosphorylated in response to growth factors that act through non-cytokine receptors, suggesting that Rul may function as a common regulator of mitogenesis.
Erythropoietin and interleukin-2 activate distinct JAK kinase family members
TLDR
It is demonstrated that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R cells and that the EPO and IL-2 receptors interact with distinct JAK kinase family members within the same cellular background.
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TLDR
The role of various kinases in this response is discussed as well as an assessment of potential substrates of tyrosine phosphorylation.
Induction of tyrosine phosphorylation by the erythropoietin receptor correlates with mitogenesis
TLDR
Two mutants of the EpoR that lacked 108 or 146 amino acids at their carboxyl termini were generated, and an internally deleted mutant that lacked 20 amino acids in a region of sequence homology with the IL-2 receptor beta chain was constructed.
Association of the erythropoietin receptor with protein tyrosine kinase activity.
TLDR
It is suggested that a 97-kDa phosphotyrosylprotein associated with the Epo receptor is a protein tyrosine kinase involved in Epo-mediated signal transduction.
In vitro phosphorylation of the erythropoietin receptor and an associated protein, pp130.
TLDR
It is shown that addition of EPO or interleukin-3 to an IL-3-dependent cell line expressing the wild-type EPOR causes a small fraction of total cellular EPOR to shift in gel mobility from 66 to 72 kDa, and that phosphorylation or interaction with a protein kinase in the carboxy-terminal region may down-modulate the proliferative action of the EPOR.
Homodimerization and constitutive activation of the erythropoietin receptor.
TLDR
Homodimerization of the EPO-R is likely to play a role in ligand-induced signal transduction, and disulfide-linked homodimers of the constitutive receptor may mimic this step.
Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity
THE receptors for erythropoietin and other cytokines constitute a new superfamily1–4. They have no tyrosine-kinase or other enzyme motif and their signal-transducing mechanism is unclear. Here we
The cytoplasmic region of the erythropoietin receptor contains nonoverlapping positive and negative growth-regulatory domains.
TLDR
A membrane-proximal positive signal transduction domain of less than or equal to 103 amino acids, in a region highly similar to the interleukin-2 receptor beta chain, was sufficient for EPO-mediated signalTransduction.
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