More Cables to Abl

Previews contains an area of weak homology to cyclin A and More Cables to Abl cyclin C. The authors went on to show that Cables bound to Cdk5 and that it could function as a substrate for phosphorylation by the Cdk5/p35 kinase. Interestingly, there appears to be some form of competition for bind-Life is complex. Take for example the abelson gene, ing to Cdk5 in that Cdk5/Cables and Cdk5/p35 protein named for the individual who discovered a transform-complexes can be detected but Cables/Cdk5/p35 trimo-ing retrovirus capable of turning normal cells into cancer lecular complexes cannot. In addition to the C-terminal cells. abl was subsequently cloned from both the virus Cdk5 binding domain, Cables has six potential SH3 and from normal cells and found to encode a cyto-binding motifs (PXXP) clustered around its N terminus, plasmic protein tyrosine kinase (PTK) that, in the onco-two of which are similar to motifs known to bind the Abl genic state, is essentially a constitutively active enzyme. SH3 domain. Biochemical tests determined that Cables Normal Abl function is very important for humans. The does bind to Abl and that a trimolecular complex of most glaring example of this is in chronic myelogenous Cdk5, Abl, and Cables exists in vivo. These results pro-leukemia (CML). Almost invariably, all people who suffer vide a critical link between Abl and Cdk5. from this cancer show the hallmark Philadelphia chro-The merging of Cdk5 and Abl pathways opens a door mosome translocation which involves the abl gene. After full of potential for speculation and future experimenta-decades of work by many scientists, great progress has tion. For instance, how does the connection between been made at identifying roles for Abl in the cell. Yet, Cdk5, Cables, and Abl fit into what we already know despite the many advances, there remains no compre-about the normal biological functions of Abl? Some of hensive model for Abl function. In addition to its PTK the earliest insights into the normal functions of Abl were catalytic domain, which phosphorylates substrates on obtained in studies with Drosophila that began in Mike tyrosine residues, Abl has a number of protein interac-Hoffmann's laboratory in the 1980s. Indeed, the first tion domains including Src homology domains 2 and 3 " cable " to Abl is a gene called disabled, whose existence (SH2 and SH3), nuclear localization signals, and DNA was pointed out 13 years ago as being a locus that, and …