Leptin Receptor B, phosphorylated (Tyr1138) (ObRb, Obese Receptor B)

Obesity, a common nutritional disorder, is associated with diabetes, hypertension, hyperlipidemia, cancer and many other health related problems. Obese gene, leptin, mediates its effects via the Leptin receptor or obese receptors (OBR or LR) that is expressed in several tissues including hypothalamus. The OBR has at least 6 alternatively spliced forms (OBRa-f or LRa-f) that contain a common extracellular domain. OBRb or long isoform contains a unique ~300aa long cytoplasmic tail that is required for leptin signaling. OBR is abnormally spliced (truncation of cytoplasmic domain) in db/db mice resulting into severe obesity.\n\nLeptin is structurally related to cytokine family and it activates cytokine-like signal transduction by stimulating the JAK-STAT pathway via the OBRb, a member of IL-6 receptor family of class I cytokine receptors. Leptin binding to OBRb results in the activation of JAK2 and subsequent phosphorylation of specific tyrosines (Tyr985 and Tyr1138) located at the C- terminal, cytoplasmic region of OBRb. Phosphorylation of OBRb Tyr1138 recruits the SH2 domain containing STAT3, its autophosphorylation, translocation to the nucleus, and modulation of gene transcription, most notably induction of suppressor of cytokine signaling 3 gene (SOCS3 or CIS3). SOCS3 inhibits leptin signaling. SOCS3 have been reported to be elevated in some obese animals. Tyr985 phosphorylation of OBRb recruits the SH2 domain containing protein-tyrosine phosphatase SHP-2, it's binding to GRB2, and subsequent activation of ERK, a group of ser/thr kinases involved in the regulation of gene transcription. Therefore, OBRb Tyr phosphorylation plays in critical role in leptin signaling.\n\nApplications:\nSuitable for use in ELISA and Western Blot. Other applications not tested.\n\nRecommended Dilution:\nELISA: 0.1-2ug/ml (10-100ng of coated peptide/well). See Catalog #L1671-13A.\nWestern Blot: 2-10ug/ml\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with sterile ddH2O or PBS. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Reconstituted product is stable for 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

L1671-13

Size

100ug

Applications

ELISA, WB

Hosts

Rabbit

Reactivities

Mouse

Form

Supplied as a lyophilized powder from PBS, 0.05% sodium azide.

P Type

Pab

Purity

Purified by immunoaffinity chromatography.

Isotype

IgG

References

1. Bjorbaek C et al (1999) J. Biol. Chem. 274, 30059; 2. Bjorbaek C et al (2000) J. Biol. Chem. 275, 40649; 3. Bank AS et al (2000) J. Biol. Chem. 275, 14563; 4. Bjorbaek C et al (1998) Mol. Cell 1, 619; 5. Tartaglia, LA (1995) Cell 83, 1263; 6. Chen H et al (1996) Cell 84, 491-495; 7. Lee GH et al (1996) Nature 379, 632-635; 8. Cioffi JA et al (1996) Nat. Med. 2, 585-589.

Additional Info

Recognizes mouse ObRb when phosphorylated at Tyr1138. Species sequence homology: rat (91%), human (64%).