Table 1. Characteristics of cortactin SH3 domain-binding proteins.
The ‘Evidence’ column lists the experimental approaches used to confirm the interaction. Amino acids in the binding site that match the cortactin SH3 binding consensus are underlined. Two binding sites were identified on Dynamin 2 and CD2AP. In the case of the latter, the second site at amino acid 392 is a lower affinity site. The binding motifs on CortBP1 and CBP90 are predicted based upon deletion analysis and similarity to the consensus sequence. CBP90, cortactin-binding protein of 90 kDa; Co-IP, co-immunoprecipitation; DZO-1, Drosophila zonnula occludens 1; N.D., not determined; Y2H, yeast two hybrid analysis.
| Protein | Class | Evidence | Cellular role | Binding site (consensus+PPΨPXKP) | Reference |
|---|---|---|---|---|---|
| CortBP1/Shank2 | Scaffold | Y2H | Organization of transmembrane protein complexes, particularly at PSD | 946 KPPVPPKP | 80 |
| GST pull-down | |||||
| Co-IP | |||||
| Co-localization | |||||
| CBP90 | Unknown | GST overlay and pull-down | Unknown | 539 PPPIPPKKP | 11 |
| DZO-1 | Scaffold | Y2H | Organization of transmembrane protein complexes at cellular tight junctions | 1194 KPVPPPKP* | 14 |
| Co-IP | |||||
| Co-localization | |||||
| Dynamin 2 | Mechano-chemical | GST overlay and pull-down | Vesicle fission in receptor-mediated endocytosis Cortical actin rearrangement | 826 PPQIPSRP† | 86 |
| GTPase | Co-IP | 849 APAAPSRP† | |||
| Co-localization | |||||
| CD2AP | Adaptor/scaffold | GST pull-down and overlay | Endocytosis and downregulation of growth factor receptors | 381 KPAAPQVP* | 79 |
| Co-IP | 392 KPTAPTKA* | ||||
| Co-localization | Organization of transmembrane receptor complexes | ||||
| Fgd1 | Cdc42 GEF | Y2H | Cortical actin organization | 158 KPQVPPKP* | 40 |
| GST overlay | Mutated in faciogenital dysplasia | ||||
| Co-localization | |||||
| Co-IP | |||||
| N-WASP | NPF | GST pull-down and overlay | Effector in Cdc42-regulated actin nucleation | N.D. | 85 |
| Co-IP | Filopodia formation | ||||
| Co-localization | |||||
| WIP | Adaptor | Y2H | Regulates N-WASP NPF activity | N.D. | 73 |
| GST pull-down | Yeast homologue Vrp1p regulates actin dynamics | ||||
| Co-IP | |||||
| Co-localization |
* Binding site confirmed by site-directed mutagenesis.
† Binding site determined by phosphopeptide competition.