Product Sheet CC1012
Description
BACKGROUND c-Abl is a non-receptor protein-tyrosine kinase related to the Src family. The N-terminal region of c-Abl is structurally similar to Src and includes Src homology regions 3 and 2 (SH3 and SH2) and the catalytic domain; however, Abl differs from all Src family members by the presence of a large (90 kDa) C-terminal domain. Several functional motifs have been defined in the Abl C-terminus, including a nuclear localization signal (NLS), DNA binding domain, actin binding domain, sites for phosphorylation by protein kinase C and cdc-2 kinase, and binding sites for the adapter proteins Crk, Grb-2 and Nck.1 c-Abl has been implicated in many cellular processes including differentiation, division, adhesion, death, and stress response. c-Abl becomes activated in response to numerous extra- and intra-cellular stimuli.2 c-Abl is localized in the nucleus and the cytoplasm, where it plays distinct roles. The effects of c-Abl are mediated by multiple protein-protein and protein-DNA interactions and its tyrosine kinase domain.3 Its oncogenic counterpart, the Bcr–Abl fusion protein, causes particular human leukaemias. Use of targeted therapy that inhibits BCR-ABL kinase activity by Gleevec leads to hematologic and cytogenetic responses in affected individuals.4
Mutation of a tyrosine (Tyr-245) in the linker region between the Src homology 2 and catalytic domains that is conserved among the Abl family inhibited the autophosphorylation-induced activation of wild-type c-Abl by 50%, whereas the c-Abl Y245F/Y412F double mutant was minimally activated by autophosphorylation. These results support a model where c-Abl is inhibited in part through an intramolecular Src homology 3-linker interaction and stimulated to full catalytic activity by sequential phosphorylation at Tyr-412 and Tyr-245.5
REFERENCES
1. Hantschel,O. & Superti-Furga, G.: Nat Rev Mol Cell Biol. 5:33-44, 2004.
2. Sirvent, A. et al: Biol Cell 100:617-631, 2008.
3. Wang, J.Y.: Nat Cell Biol. 6:3-7, 2004.
4. Curran, M. P. et al: Biodrugs, 18:207-210, 2004.
5. Brasher, B. B. & Van Etten, R. A.: J. Biol. Chem., 275:35631-7, 2000.
1. Hantschel,O. & Superti-Furga, G.: Nat Rev Mol Cell Biol. 5:33-44, 2004.
2. Sirvent, A. et al: Biol Cell 100:617-631, 2008.
3. Wang, J.Y.: Nat Cell Biol. 6:3-7, 2004.
4. Curran, M. P. et al: Biodrugs, 18:207-210, 2004.
5. Brasher, B. B. & Van Etten, R. A.: J. Biol. Chem., 275:35631-7, 2000.
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
(Click to Enlarge) The K562 cells were treated with Gleevec and applied onto Western blot analysis using Phospho-c-Abl (Tyr245) Antibody (top), or c-Abl Antibody (bottom).
Details
Cat.No.: | CC1012 |
Antigen: | An epitope surrounding and including Tyr245 of human c-Abl. |
Isotype: | Rabbit polyclonal IgG |
Species & predicted species cross- reactivity ( ): | Human, Mouse, Rat |
Applications & Suggested starting dilutions: | WB 1:1000 IP n/d IHC (Paraffin) n/d ICC n/d FACS n/d |
Predicted Molecular Weight of protein: | 140 kDa |
Specificity/Sensitivity: | This affinity purified antibody detects endogenous Phospho-c-Abl in cell lysates. |
Storage: | Store at -20°C, 4°C for frequent use. Avoid repeated freeze-thaw cycles. |
*Optimal working dilutions must be determined by end user.
Products
| Product | Size | CAT.# | Price | Quantity |
|---|---|---|---|---|
| Polyclonal c-Abl, Phospho-Tyr245 Antibody: Polyclonal c-Abl, Phospho-Tyr245 Antibody | Size: 100 ul | CAT.#: CC1012 | Price: $333.00 |