Cell Signaling Technology

Product Pathways - Tyrosine Kinase / Adaptors

Phospho-Gab2 (Tyr452) (C33G1) Rabbit mAb #3882

Applications Reactivity Sensitivity MW (kDa) Isotype
W H M Endogenous 98 Rabbit IgG

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  M=Mouse
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Phospho-Gab2 (Tyr452) (C33G1) Rabbit mAb detects endogenous levels of Gab2 only when phosphorylated at Tyr452. This antibody weakly cross-reacts with tyrosine-phosphorylated Gab1 and Gab3 proteins.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr452 of human Gab2.

Western Blotting

Western Blotting

Western blot analysis of extracts from Baf3 cells stably transfected with a construct expressing FLT3, untreated or treated with FLT ligand (FL), using Phospho-Gab2 (Tyr452) (C33G1) Rabbit mAb (upper) or Gab2 (26B6) Rabbit mAb #3239 (lower).

Background

The Grb-associated binder (Gab) family is a family of adaptor proteins recruited by a wide variety of receptor tyrosine kinases (RTKs) such as EGFR, HGFR, insulin receptor, cytokine receptor and B cell antigen receptors. Upon stimulation of RTKs by their cognate ligand, Gab is recruited to the plasma membrane where it is phosphorylated and functions as a scaffold (1-4). Multiple tyrosine phosphorylation sites of Gab1 protein have been identified (5). Phosphorylation of Tyr472 regulates its binding to p85 PI3 kinase (6,7). Phosphorylation of Gab1 at Tyr307, Tyr373 and Tyr407 modulates its association to PLCγ (8). Phosphorylation of Tyr627 and Tyr659 is required for Gab1 binding to and activation of the protein tyrosine phosphatase SHP2 (6,9).

Gab2 is also phosphorylated by tyrosine kinases (10,11). Tyr452 is a potential binding site of p85, the regulatory subunit of PI3 kinase (12). Tyr614 is essential for SHP2 association (11). Furthermore, Akt phosphorylates Gab2 at Ser159 and inhibits Gab2 tyrosine phosphorylation, suggesting that Akt is engaged in negative feedback regulation of Gab2 signaling (13).

  1. Holgado-Madruga, M. et al. (1996) Nature 379, 560-564.
  2. Weidner, K.M. et al. (1996) Nature 384, 173-176.
  3. Takahashi-Tezuka, M. et al. (1998) Mol. Cell. Biol. 18, 4109-4117.
  4. Ingham, R.J. et al. (2001) J Biol Chem 276, 12257-65.
  5. Lehr, S. et al. (1999) Biochemistry 38, 151-159.
  6. Rocchi, S. et al. (1998) Mol. Endocrinol. 12, 914-923.
  7. Yu, C.F. et al. (2001) J Biol Chem 276, 32552-8.
  8. Gual, P. et al. (2000) Oncogene 19, 1509-18.
  9. Cunnick, J.M. et al. (2001) J Biol Chem 276, 24380-7.
  10. Gadina, M. et al. (2000) J. Biol. Chem. 275, 26959-26966.
  11. Yamasaki, S. et al. (2001) J. Biol. Chem. 276, 45175-451783.
  12. Crouin, C. et al. (2001) FEBS Lett. 495, 148-153.
  13. Lynch, D.K. and Daly, R.J. (2002) EMBO J. 21, 72-82.

Application References

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For Research Use Only. Not For Use In Diagnostic Procedures.

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