Cell Signaling Technology

Product Pathways - TGF-beta/Smad Signaling

Smurf1 Antibody #2174

Applications Reactivity Sensitivity MW (kDa) Source
W H Endogenous 81 Rabbit

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

Specificity / Sensitivity

Smurf1 Antibody detects endogenous levels of total Smurf1 protein.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to a central region within human Smurf1 protein. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using Smurf1 Antibody.

Background

Bone morphogenetic proteins (BMPs) constitute a large family of signaling molecules that regulate a wide range of critical processes including morphogenesis, cell-fate determination, proliferation, differentiation, and apoptosis (1,2). BMP receptors are members of the TGF-β family of Ser/Thr kinase receptors. Ligand binding induces multimerization, autophosphorylation, and activation of these receptors (3-5). They subsequently phosphorylate Smad1 at Ser463 and Ser465 in the carboxy-terminal motif SSXS, as well as Smad5 and Smad8 at their corresponding sites. These phosphorylated Smads dimerize with the coactivating Smad4 and translocate to the nucleus, where they stimulate transcription of target genes (5).MAP kinases and CDKs 8 and 9 phosphorylate residues in the linker region of Smad1, including Ser206. The phosphorylation of Ser206 recruits Smurf1 to the linker region and leads to the degradation of Smad1 (6). Phosphorylation of this site also promotes Smad1 transcriptional action by recruiting YAP to the linker region (7).

Smurf1, a member of the HECT family of E3 ubiquitin ligases, selectively interacts with BMP pathway Smad effectors, leading to Smad protein ubiquitination and degradation (6). In addition, Smurf1 interacts with the inhibitor Smad, Smad7, the bone-specific transcription factor Runx2/Cbfa1, RhoA and MEKK2 (7-10). Smurf1 negatively regulates osteoblast differentiation and bone formation in vivo (10,11). A related protein, Smurf2, acts more promiscuously, interacting with both BMP and TGF-β pathway Smad proteins (12).

  1. Hogan, B.L. et al. (1996) Genes Dev. 10, 1580-1594.
  2. Hoodless, P.A. et al. (1996) Cell 85, 489-500.
  3. Klemm, J.D. et al. (1998) Annu. Rev. Immunol. 16, 569-592.
  4. Kretzschmar, M. et al. (1997) Genes Dev. 11, 984-995.
  5. Whitman, M. (1998) Genes Dev. 12, 2445-2462.
  6. Sapkota, G. et al. (2007) Mol Cell 25, 441-54.
  7. Alarcón, C. et al. (2009) Cell 139, 757-69.
  8. Zhu, H. et al. (1999) Nature 400, 687-693.
  9. Ebisawa, T. et al. (2001) J. Biol. Chem. 276, 12477-12480.
  10. Zhao, M. et al. (2003) J. Biol. Chem. 278, 27939-27944.
  11. Wang, H.R. et al. (2003) Science 302, 1775-1779.
  12. Yamashita, M. et al. (2005) Cell 121, 101-113.
  13. Zhao, M. et al. (2004) J. Biol. Chem. 279, 12854-12859.
  14. Zhang, Y. et al. (2001) Proc. Natl. Acad. Sci. U S A 98, 974-979.

Application References

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Companion Products

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

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