A Hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors
Article first published online: 25 DEC 2001
Genes to Cells
Volume 5, Issue 1, pages 57–69, January 2000
How to Cite
Takata, H., Kato, M., Denda, K. and Kitamura, N. (2000), A Hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors. Genes to Cells, 5: 57–69. doi: 10.1046/j.1365-2443.2000.00303.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Cited By
Hrs (hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate) is an early endosomal protein that is rapidly tyrosine-phosphorylated in cells stimulated with growth factors. Hrs is thought to play a regulatory role in the endocytosis of growth factor/receptor complexes through early endosomes. In this study, we searched for Hrs-interacting molecules which may regulate the function of Hrs, using a yeast two-hybrid system.
We isolated a cDNA clone encoding a novel Src homology 3 (SH3)-containing protein, and named it ‘Hrs binding protein’ (Hbp). Hbp was co-immunoprecipitated with Hrs, and its intracellular localization was similar to that of Hrs. The association between Hbp and Hrs was mediated through the coiled coil motifs in Hbp and Hrs. Deletion mutants of Hbp lacking either the SH3 domain or the Hrs binding domain showed dominantly negative effects on the intracellular degradation of a growth factor and its receptor, but not on the internalization of growth factor/receptor complexes.
Hbp is thought to be closely associated with Hrs on early endosomes. Hbp, together with Hrs may play a regulatory role in the vesicular transport of growth factor/receptor complexes through early endosomes, for their degradation.