Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H||WB||Rb||Affinity Purified||Polyclonal Antibody|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Maintain at -20°C in undiluted for up to 6 months after date of receipt. Avoid repeated freeze/thaw cycles. Do not store in a self defrosting freezer.|
|Material Size||100 µL|
|Material Package||10 Blots|
|Reference overview||Pub Med ID|
|Lipopolysaccharide-induced tau phosphorylation and kinase activity--modulation, but not mediation, by corticotropin-releasing factor receptors. |
Allyson D Roe,Michael A Staup,Jordi Serrats,Paul E Sawchenko,Robert A Rissman
The European journal of neuroscience 34 2011
Clinical studies suggest that exposure to stress can increase risk for Alzheimer's disease (AD). Although the precise links between stress and vulnerability to develop AD remain uncertain, recent animal work suggests that stress may promote susceptibility to AD pathology by activating tau kinases and inducing tau phosphorylation (tau-P). Our previous findings indicate the differential involvement of corticotropin-releasing factor receptor (CRFR) types 1 and 2 in regulating tau-P in the hippocampus induced by acute restraint, an emotional stressor. To assess the generality of CRFR involvement in stress-induced tau-P and tau kinase activity, the present study extends our investigation to a well-characterized physiological stressor, i.e. immune challenge induced by bacterial lipopolysaccharide (LPS). Acute systemic administration of LPS (100 μg/kg) robustly increased hippocampal (but not isocortical or cerebellar) tau-P, peaking at 40-120 min postinjection and abating thereafter. Assessments of the genotype dependence of this effect yielded results that were distinct from the restraint model. Treatment with LPS increased phosphorylation in wild-type, single and double CRFR knockouts with only subtle variation, which included a reliable exaggeration of tau-P responses in CRFR1-deficient mice. Parallel analyses implicated glycogen synthase kinase-3 and cyclin-dependent kinase-5 as likely cellular mediators of LPS-induced tau-P. Conversely, our data suggest that temperature-dependent fluctuations in tau protein phosphatase 2A (PP2A) may not play a role in this context. Thus, neither the strict CRFR1 dependence of restraint-induced tau-P nor the exaggeration of these responses in CRFR2 null mice generalize to the LPS model. CRFR mediation of stress-induced hippocampal tau-P may be limited to emotional stressors.
|Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. |
Augustinack, J.C., et al.
Acta Neuropathol., 103:26-35 (2002) 2002
|Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. |
Kins, S., et al.
J. Biol. Sci., 276(41):38193-200 (2001) 2001
|Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. |
Gong, C.X., et al.
J. Biol. Chem., 275(8):5535-5544 (2000) 2000
|Phosphorylated serine 422 on tau proteins is a pathological epitope found in several diseases with neurofibrillary degeneration. |
Bussiere, T., et al.
Acta Neuropathol., 97(3):221-30 (1999) 1999
|Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau protein. |
Reynolds, C H, et al.
J. Neurochem., 68: 1736-44 (1997) 1997
A proportion of the neuronal microtubule-associated protein (MAP) tau is highly phosphorylated in foetal and adult brain, whereas the majority of tau in the neurofibrillary tangles of Alzheimer's patients is hyperphosphorylated; many of the phosphorylation sites are serines or threonines followed by prolines. Several kinases phosphorylate tau at such sites in vitro. We have now shown that purified recombinant stress-activated protein kinase/c-Jun N-terminal kinase, a proline-directed kinase of the MAP kinase extended family, phosphorylates recombinant tau in vitro on threonine and serine residues. Western blots using antibodies to phosphorylation-dependent tau epitopes demonstrated that phosphorylation occurs in both of the main phosphorylated regions of tau protein. Unlike glycogen synthase kinase-3, the c-Jun N-terminal kinase readily phosphorylates Thr205 and Ser422, which are more highly phosphorylated in Alzheimer tau than in foetal or adult tau. Glycogen synthase kinase-3 may preferentially phosphorylate the sites found physiologically, in foetal and to a smaller extent in adult tau, whereas stress-activated/c-Jun N-terminal kinase and/or other members of the extended MAP kinase family may be responsible for pathological proline-directed phosphorylations. Inflammatory processes in Alzheimer brain might therefore contribute directly to the pathological formation of the hyperphosphorylated tau found in neurofibrillary tangles.
|RABBIT ANTI-Tau phosphoSerine 422 POLYCLONAL ANTIBODY|