Product Pathways - Tyrosine Kinase / Adaptors
Bcr-Abl (b2a2 Junction Specific) (L99H4) Mouse mAb #3908
PhosphoSitePlus® protein, site, and accession data: Bcr/Abl
| Applications | Reactivity | Sensitivity | MW (kDa) | Isotype |
|---|---|---|---|---|
| W | H | Endogenous | 210 | Mouse IgG2a |
Applications Key:
W=Western Blotting
Reactivity Key:
H=Human
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.
Protocols
- 3908:
- Western Blotting
Specificity / Sensitivity
Bcr-Abl (b2a2 Junction Specific) (L99H4) Mouse mAb detects endogenous levels of Bcr-Abl (b2a2) fusion proteins. This antibody does not cross-react with the b3a2 isoform of Bcr-Abl.
Source / Purification
Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to the b2a2 junction site sequence of human Bcr-Abl.
Background
The Bcr gene was orginally identified by its presence in the chimeric Bcr-Abl oncogene (1). The amino-terminal region of Bcr contains an oligomerization domain, a serine/threonine kinase domain, and a region that binds SH2 domains. The middle of the protein has a PH domain and a region of sequence similarity to the guanine nucleotide exchange factors for the Rho family of GTP binding proteins. The carboxy-terminal region may be involved in a GTPase activating function for the small GTP-binding protein Rac (2,3). The function of wild type Bcr in cells remains unclear. PDGF receptor may use Bcr as a downstream signaling mediator (4). Research studies have shown that the Bcr-Abl fusion results in production of a constitutively active tyrosine kinase, which causes chronic myelogenous leukemia (CML) (5). Tyr177 of Bcr is phosphorylated in the Bcr-Abl fusion protein, which plays an important role in transforming the activity of Bcr-Abl (6). Phosphorylated Tyr177 provides a docking site for Gab2 and GRB2 (7,8).
The fusion protein encoded by Bcr-Abl varies in size, depending on the breakpoint in the BCR gene. Three breakpoint cluster regions have been characterized to date: major (M-bcr), minor (m-bcr) and micro (mu-bcr). The overwhelming majority of CML patients have a p210 Bcr-Abl gene (M-bcr), whose mRNA transcripts have a b3a2 and/or a b2a2 junction. The smallest of the fusion proteins, p190 Bcr-Abl, (m-bcr breakpoint) is principally associated with Ph-positive ALL. Rare cases of CML are due to a p190-type of Bcr-Abl gene and in these, the disease tends to have a prominent monocytic component, resembling CMML. CML resulting from a p230 Bcr-Abl gene (mu-bcr breakpoint) is also rare, and has been associated with the CNL variant and/or with marked thrombocytosis. Exceptional CML cases have been described with Bcr breakpoints outside the three defined cluster regions, or with unusual breakpoints in Abl (9).
- Groffen, J. et al. (1984) Cell 36, 93-99.
- Maru, Y. et al. (1991) Cell 67, 459-468.
- Che, W. et al. (2001) Circulation 104, 1399-1406.
- Abe, J. I. et al. (2001) Ann. N.Y. Acad. Sci. 947, 341-343.
- Voncken, J. W. et al. (1995) Cell 80, 719-728.
- He, Y. et al. (2002) Blood 99, 2957-2968.
- Sattler, M. et al. (2002) Cancer Cell 1, 479-492.
- Warmuth, M. et al. (1995) J. Biol. Chem. 272, 33260-33270.
- Melo, J.V. (1997) Baillieres Clin. Haematol 10, 203-22.
Application References
Have you published research involving the use of our products? If so we'd love to hear about it. Please let us know!
Companion Products
- 3901 Phospho-Bcr (Tyr177) Antibody
- 3902 Bcr Antibody
- 7072 Phototope®-HRP Western Blot Detection System, Anti-mouse IgG, HRP-linked Antibody
- 7076 Anti-mouse IgG, HRP-linked Antibody
- 7720 Prestained Protein Marker, Broad Range (Premixed Format)
- 7727 Biotinylated Protein Ladder Detection Pack
- 7003 20X LumiGLO® Reagent and 20X Peroxide
For Research Use Only. Not For Use In Diagnostic Procedures.