IndraLab
Statements
rlimsp
"There is also evidence to the contrary, as the SH2 domain of SH2-Bβ was sufficient to activate Jak2 in a different experimental context 15,16; if so, the biphasic dependence of Jak2 autophosphorylation on SH2-Bβ concentration might be attributed to a second, inhibitory interaction involving the PH domain."
rlimsp
"Besides the bipolar clamp mechanism explored here, it has also been postulated that SH2-Bβ binding is sufficient for enhancing Jak2 catalytic efficiency [16], and this alternative mechanism might account for the apparent ability of SH2-Bβ to enhance Jak2 autophosphorylation in solution and in unstimulated cells (with Jak2 overexpressed) [14]."
rlimsp
"Tkip (WLVFFVIFYFFR), a suppressor of cytokine signalling (SOCS)-1 mimetic peptide that inhibits JAK2 autophosphorylation, was generously provided by Dr Howard M Johnson (Institute of Food and Agricultural Science, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA)."
reach
"Upon inhibition of the phosphorylation of JAK2/STAT3 by the JAK2/STAT3 inhibitor AG490, the up-regulated expression and translocation of HMGB1 was reduced and EBI was ameliorated, further highlighting the contribution of JAK2/STAT3 pathway in HMGB1-mediated neuroinflammation in SAH [76]."
sparser
"EPO binding to the EPO-receptor triggers activation of JAK2 and phosphorylated JAK2 can bind to STAT5 wherein the JAK2-STAT5 complex translocates to the nucleus and induces expression of target genes xref including but not limited to IREB2 (Iron responsive element binding protein 2) and anti-apoptotic factors such as BCL-XL xref ."
reach
"Overall these results show that extracellular ligands that enforce large receptor dimer separation and different binding geometries can counteract intracellular oncogenic ligand independent receptor activation, presumably by exceeding the accessible distance that the JAK2 kinase domain can extend to transphosphorylate the opposing JAK2 and receptor (XREF_FIG)."
rlimsp
"At least in the context of our models, it is incorrect to characterize SH2-Bβ dimerization as a means of bringing two Jak2 molecules together, as might be inferred by the ability of the adaptor to enhance Jak2 autophosphorylation in solution; rather, we suggest that it acts as a clamp that stabilizes existing J(RLR)J complexes."
reach
"Taken together, these data showed that the JAK2 associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS."
| PMC
reach
"Because Stat3 activation is primarily mediated by Jak2, XREF_BIBR the levels of Jak2 phosphorylation, Stat3 tyrosine 705 phosphorylation (a primary activating phosphorylation site on Stat3), and the expression levels of Stat3 were assessed in the cells treated with selected strong anti-Stat3 herbal extracts."
sparser
"In addition, we measured the expression of JAK2 and phosphorylated JAK2, STAT3 and phosphorylated STAT3 after treating both cell lines with the combination of DXM and AG490, and we could not detect significant change in the expression of these proteins compared with AG490 alone (data not shown)."
reach
"Stimulation of the long receptor isoform by leptin leads to phosphorylation of Janus kinase 2 (JAK2), followed by phosphorylation of tyrosine residues 985 and 1138, which activate a series of pathways, namely, phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription 3 (STAT3) (33) ."
rlimsp
"As an additional approach, based on a different mechanism of inhibition, we designed a P1 (Penetratin-1)-coupled peptide, carrying the already described tyrosine kinase inhibitor peptide (TKIP) sequence (Flowers et al., 2004), blocking selectively JAK2 autophosphorylation and activation."
reach
"The binding of GH to cell surface homodimeric GHR, a type I cytokine receptor lacking intrinsic tyrosine kinase activities, initiates Janus kinase 2 (JAK2)-dependent (8) signal transduction, in which JAK2 phosphorylates the 7 tyrosines within the human GHR intracellular domain (9), and phosphorylates signaling components recruited to the activated GHR (Figure 1)."
rlimsp
"The JAK2V617F mutation leads to autophosphorylation of JAK2 and constitutive activation of downstream pathways including the Janus kinase (JAK)/STAT, phosphatidylinositol 3 kinase/AKT (v-akt murine thymoma viral oncogene homolog 1) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase pathways."
reach
"6 In murine models and patients with beta-thalassemia, erythroid precursors express elevated levels of the phosphorylated active form of Jak2 (pJak2), and other downstream signaling molecules that promote proliferation and inhibit differentiation of erythroid progenitor cells (XREF_FIG)."
rlimsp
"We herein demonstrated that protein tyrosine phosphatase receptor type J (Ptprj) is expressed in hypothalamic neurons together with leptin receptors, and that PTPRJ negatively regulates leptin signaling by inhibiting the activation of JAK2, the primary tyrosine kinase in leptin signaling, through the dephosphorylation of Y813 and Y868 in JAK2 autophosphorylation sites."
rlimsp
"The P1-TKIP peptide (RQIKIWFQNRRMKWKKGWLVFFVIFYFFR; underlined letter highlights the important inserted glycine allowing flexibility of the fusion peptide) encompassed the complete P1 sequence (16 aa), an inserted glycine to allow flexibility of the fusion peptide, and the TKIP sequence (12 aa) blocking specifically JAK2 autophosphorylation (Flowers et al., 2004)."
rlimsp
"Intuitively, one might expect that membrane localization of SH2-Bβ would drive significantly more Jak2 into complex with receptors; however, this was not the case with the DD present (Figure 5B), and accordingly, Jak2 autophosphorylation was not dramatically enhanced by SH2-Bβ with the DD absent, even with arbitrarily high SH2-Bβ and phosphoinositide concentrations (Figure 5C and 5D)."