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Historical Research

Adaptor proteins

Adaptor proteins are known to function as connecting links between different signaling proteins. They facilitate signal transduction by providing a scaffold for protein assembly and can decide when and where a specific enzyme like protein kinase, will become activated.

The Crk family consists of CrkI, CrkII and CrkL adaptor proteins, which engage multiple signaling pathways through the SH2 and SH3 domains and link upstream tyrosine kinase dependent signals to downstream effectors.

Although there are many studies describing the important role of Crk proteins in regulation of key cellular processes including cell motility, phagocytosis, proliferation, transformation and apoptosis as well as its essential role in many human cancers, a mechanistic understanding of Crk proteins remains elusive.

Considering the high sequence identity between CrkL and CrkII and taking into account their identical binding preferences, it was hypothesized that these two proteins adopted very similar structures and regulatory mechanisms. In this light, however, it was difficult to justify why Crk proteins have distinct, non-overlapping functions.

In a recent work Professor Kalodimos and graduate students Wojciech Jankowski and Tamjeed Saleh demonstrated that structural organization between CrkL and CrkII is considerably different. Researchers explained how the distinct structural architecture determines the different physiological functions for these two proteins. The data show that CrkL, unlike CrkII forms a constitutive complex with Abl thus explaining the strong preference of Bcr-Abl for CrkL. These results are now published in Nature Chemical Biology and were discussed on News and Views by Kobashigawa and Inagaki.

Year of Research Highlight: 2012

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