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
"This alternative mechanism might also complement the bipolar clamp function of SH2-Bβ, but only in cells where Jak2 in J(RLR)J complexes (without SH2-Bβ bound) tends to be dephosphorylated, at least on certain sites (it is important to bear in mind that Tyr813 must be autophosphorylated in order for SH2-Bβ to bind; see Figure S2B, Supporting Information)."
"The jak2 jh2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of jak2 remains unknown. Here we show that jh2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in jak2: ser523 and tyr570."
rlimsp
"Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity. Janus kinase 2 (JAK2) is activated by a majority of cytokine family receptors including receptors for GH, leptin, and erythropoietin. To identify novel JAK2-regulatory and/or -binding sites, we set out to identify autophosphorylation sites in the kinase domain of JAK2. Two-dimensional phosphopeptide mapping of in vitro autophosphorylated JAK2 identified tyrosines 868, 966, and 972 as sites of autophosphorylation."
"The jak2 jh2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of jak2 remains unknown. Here we show that jh2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in jak2: ser523 and tyr570."
"Analysis of in vitro autophosphorylated jak2while cytokine receptor stimulation mediates the phosphorylation of both tyr317 and tyr637, these residues oppositely regulate jak2-dependent signaling: the mutation of tyr317 enhances jak2 function, suggesting a role for the phosphorylation of tyr317 in the inhibition of jak2. Conversely, mutation of tyr637 reduces jak2 signaling, suggesting a role for the phosphorylation of this residue in the activation of jak2."
"Analysis of in vitro autophosphorylated jak2while cytokine receptor stimulation mediates the phosphorylation of both tyr317 and tyr637, these residues oppositely regulate jak2-dependent signaling: the mutation of tyr317 enhances jak2 function, suggesting a role for the phosphorylation of tyr317 in the inhibition of jak2. Conversely, mutation of tyr637 reduces jak2 signaling, suggesting a role for the phosphorylation of this residue in the activation of jak2."
"SIRP is a transmembrane protein that is now known to bind to integrin-associated protein. It appears to bind directly to JAK2 by a process that does not require tyrosyl phosphorylation, although is itself highly phosphorylated on tyrosines in response to GH. The phosphorylated SIRP recruits one or more molecules of the tyrosine phosphatase SHP2 that, in turn, de-phosphorylates SIRP and most likely JAK2."
reach
"Importantly, basal protein expression levels of DDR1 as well as constitutive phosphorylation of JAK2 and ERK1/2 were reduced in NHLFs in the presence of DDR2 specific siRNA, suggesting a link between DDR2 activation, JAK2 and ERK1/2 phosphorylation, and DDR1 expression [XREF_BIBR]."