Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1.
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Koo DH, McFadden C, Huang Y, Abdulhussein R, Friese-Hamim M, Vogel WF
Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1.
FEBS Lett. 2006 Jan 9;580(1):15-22. Epub 2005 Dec 1.
- PubMed ID
- 16337946 [ View in PubMed]
- Abstract
Activation of the receptor tyrosine kinase DDR1 by collagen results in robust and sustained phosphorylation, however little is known about its downstream mediators. Using phosphopeptide mapping and site-directed mutagenesis, we here identified multiple tyrosine phosphorylation sites within DDR1. We found that Nck2 and Shp-2, two SH2 domain-containing proteins, bind to DDR1 in a collagen-dependent manner. The binding site of Shp-2 was mapped to tyrosine-740 of DDR1 within an ITIM-consensus sequence. Lastly, ablation of DDR1 in the mouse mammary gland resulted in delocalized expression of Nck2, suggesting that defects observed during alveologenesis are caused by the lack of the DDR1-Nck2 interaction.