The proto-oncogene c-abl was first isolated from the mouse genome as a gene with similarity to the v-abl oncogene of Abelson murine leukemia virus. The c-abl gene encodes a protein tyrosine kinase that is localized in the cytoplasm and nucleus. The c-abl protein shares several common features with other cytoplasmic tyrosine kinases, including the src-homology domains 2 (SH2) and 3 (SH3). The SH2 domain is believed to bind specifically to tyrosine residues of other proteins. The function of the SH3 domain is still unclear. Unique to the c-abl tyrosine kinase is a large C-terminal segment which seems to be essential for its biological function, since mice homozygous for a C-terminal deletion of c-abl have multiple defects at birth. The C-terminal fragment of c-abl contains a DNA-binding domain, and the DNA-binding affinity of this domain seems to be regulated by phosphorylation of critical serine/threonine residues. The c-abl proto-oncogene can be activated in a variety of ways. For example, in Philadelphia chromosome (Ph1)-positive leukemias the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and bcr-abl fusion proteins are produced. Ph1-positive cells express either the a-typical 210 kDa bcr-abl fusion protein or a smaller 185 kDa bcr-abl fusion protein. The bcr sequences activate the c-abl tyrosine kinase by deregulating its expression, and actin filament-binding function associated with c-abl is also activated. Expression of bcr-abl fusion proteins in vitro leads to transformation of pre-B lymphoid cells supporting their role as an oncogene. The phosphorylated form of c-abl is observed at ~145 kDa on SDS/PAGE. The 8E9 clone has been reported to react with an epitope in the tyrosine kinase domain of murine abl proteins [Wang et al.].
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.