Abstract
As the role for adaptor proteins constantly proliferates, appreciation of their importance has never been higher. The Crk family of adaptor proteins is no exception. Currently comprising four members, v-Crk, CrkI, CrkII and Crk-like protein, we have introduced a fifth member, CrkIII. Cloned by the CORT technique, CrkIII is identical in sequence to CrkII until the second of its two SH3 domains, which is disrupted partway through and results in a nonfunctional domain and a unique C-terminal sequence. We have demonstrated the existence of native CrkIII at the message level using RT–PCR and RNAse protection assays, and at the protein level in mouse fibroblasts. We show that CrkII overexpression is capable of enhancing insulin-stimulated ERK activity, whereas CrkIII is not, thus partially characterizing a novel member of the Crk family and elucidating important effects mediated by the c-terminal SH3 domain.
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Acknowledgements
This work was supported by National Institutes of Health Grants HL22563, DK 41684, a grant from the A and V Meinerz Foundation and by the Cancer Centre of the Medical College of Wisconsin. Dr PP is the recipient of the National Research Service Award HL10165-01. We also thank Dr Benjamin L Margolis (University of Michigan, Ann Arbor, USA), who participated in the early stages of this project and Dr Michael J Dunn (Medical College of Wisconsin, Milwaukee, USA) for his continuous support and advice.
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Prosser, S., Sorokina, E., Pratt, P. et al. CrkIII: a novel and biologically distinct member of the Crk family of adaptor proteins. Oncogene 22, 4799–4806 (2003). https://doi.org/10.1038/sj.onc.1206714
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DOI: https://doi.org/10.1038/sj.onc.1206714
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