Dab1, phosphorylated (Ser491) (Disabled homolog 1 Drosophila, Scm, Scr, Scrambler, Yot, Yotari)

Disabled 1 (Dab1) is an 80kD protein that is encoded by the Disabled-1 gene locus which is mutated in scrambler and yotari mutant mice. Phenotypically, the mutation of this gene produces motor defects and ataxia, disruption of neuronal migration and severe cerebellar hypoplasia. Dab1 is an intracellular adapter protein that functions in downstream signaling events initiated by the secreted protein reelin. Dab1 contains a phosphotyrosine binding (PTB) domain in the amino terminus. Tyrosine phosphorylation of Dab1 is increased by reelin binding to the Very Low Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2) through stimulation of Src family kinases (e.g., Fyn). Src family kinase and c-Abl activities are themselves then stimulated by binding to tyrosine phosphorylated Dab1. Dab1 also mediates activation of Akt (PKB) by reelin resulting in inhibition of glycogen synthase kinase 3b (GSK-3b) and decreased phosphorylation of the microtubule-associated protein, Tau. Dab1 serine 491 is phosphorylated in a Cdk5-dependent manner and regulates, likely indirectly, Reelin-induced signaling during neural cortex development.\n\nApplications: \nSuitable for use in ELISA and Western Blot. Other applications not tested.\n\nRecommended Dilution:\nWestern Blot: 1:1000 When examining phosphorylation of endogenous Dab1 protein it is recommended that Dab1 protein first be immunoprecipitated.\nOptimal dilutions to be determined by the researcher.\n\nPositive Control: \nHuman Embryonic Kidney (HEK293) cells transfected with wild-type mouse Dab1 protein.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. For long-term storage, aliquot and store at -20 degrees C. Aliquots are stable for at least 12 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

D0900-15

Size

10 Blots

Applications

ELISA, WB

Hosts

Rabbit

Reactivities

Hum

Form

Supplied as a liquid in Dulbecco

P Type

Pab

Purity

Purified by Protein A affinity chromatography

Isotype

IgG

References

1. Arnaud, L., et al. (2003) Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development. Curr. Biol. 13(1):9-17. 2. Beffert, U., et al. (2002) Reelin-mediated signaling locally regulates protein kinase B/Akt and glycogen synthase kinase 3b. J. Biol. Chem. 277(51):49958-49964. 3. Keshvara, L., et al. (2002) Cyclin-dependent kinase 5 phosphorylates Disabled 1 independently of Reelin signaling. J. Neurosci. 22(12):4869-4877. 4. Keshvara, L., et al. (2001) Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1. J. Biol. Chem. 276(19):16008-16014. 5. Howell, B.W., et al. (2000) Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development. Curr. Biol. 10(15):877-885. 6. Hiesberger, T., et al. (1999) Direct binding of reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron 24(2):481-489. 7. Homayouni, R., et al. (1999) Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1. J. Neurosci. 19(17):7507-7515. 8. Howell, B.W., et al. (1999) Reelin-induced tyrosine phosphorylation of disabled 1 during neuronal positioning. Genes Dev. 13(6):643-648.

Additional Info

Recognizes human Dab1 when phoshorylated at Ser491. Species sequence homology: Mouse, rat and chicken