Identification of a novel 135-kDa Grb2-binding protein in osteoclasts.

The Journal of Biological Chemistry
M SahniJ B Levy

Abstract

The tyrosine kinase receptor for macrophage colony-stimulating factor and the non-receptor tyrosine kinase c-Src play critical roles in osteoclast differentiation and function. Since the ubiquitously expressed adaptor protein Grb2 plays an important role in several tyrosine kinase signal transduction pathways, we used a filter binding assay to identify osteoclast proteins that bind to Grb2. In osteoclasts, there were three major Grb2-binding proteins, two of which, mSos and c-Cbl (p120), have been previously identified as Grb2-binding proteins in many cell types. The third protein, p135, had a restricted pattern of expression and was present at high levels in authentic osteoclasts and osteoclast-like cells formed in an in vitro co-culture system. In addition to binding Grb2 in the filter binding assay, p135 was isolated in complexes with endogenous Grb2 from osteoclast cell extracts. The association of p135 and Grb2 was dependent on an intact Src homology 3 domain and furthermore, was shown to preferentially interact with the N-terminal Src homology 3 domain of Grb2, which is similar to the interaction of mSos and Grb2 in other cell types. p135 was not recognized by antibodies against several known Grb2-binding proteins and thu...Continue Reading

References

Nov 1, 1992·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·T AkatsuT Suda
Jul 31, 1992·Biochemical and Biophysical Research Communications·K TezukaM Kumegawa
Oct 1, 1992·The Journal of Clinical Investigation·B F BoyceG R Mundy
Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J McGladeT Pawson
Oct 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·W HofstetterC Mueller
Sep 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·N TakahashiT Suda
Nov 1, 1988·Endocrinology·N TakahashiT Suda
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J S HerskovitsR B Vallee
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·P S McPhersonP De Camilli
Aug 1, 1993·The Journal of Cell Biology·A M van der BliekS L Schmid
Nov 1, 1993·The Journal of Experimental Medicine·K FullerT J Chambers
Dec 1, 1993·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·E C WeirK L Insogna
Jul 16, 1993·Cell·D Bar-SagiJ Schlessinger
Aug 1, 1993·The Journal of Cell Biology·J S HerskovitsR B Vallee

❮ Previous
Next ❯

Citations

May 6, 2005·Molecular Biology of the Cell·Angela BruzzanitiRoland Baron
Jul 16, 2008·Expert Opinion on Therapeutic Targets·Alessio GiubellinoDonald P Bottaro
Jul 13, 2006·The Journal of Biological Chemistry·John C EdwardsPaul H Schlesinger

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.