Releasing the Brake: Targeting Cbl-b to Enhance Lymphocyte Effector Functions

Figure 1

The mammalian Cbl protein family. Schematic representation of the domain architecture of the three mammalian Cbl isoforms, c-Cbl, Cbl-b, and Cbl-c/Cbl-3. The Cbl proteins are highly conserved in the N-terminal region where they comprise a tyrosine-kinase-binding domain (TKB), which is composed of a 4-helix bundle (4H), a calcium-binding EF domain, and a variant SH2 domain that is linked with the RING finger domain. The COOH-terminal region contains proline-rich stretches, multiple serine and tyrosine phosphorylation sites and a ubiquitin-associated UBA domain, and a leucine zipper. The Cbl-c isoform lacks the UBA domain and the leucine zipper domain. TKB, tyrosine-kinase-binding domain; 4H, four-helix bundle; EF, EF hand; SH2, Src-homology domain 2; R, RING “really interesting new gene” finger domain; PR, proline rich domain; Y, tyrosine residue; S, serine residue; LZ/UBA, leucine zipper/ubiquitin associated domain.