Fly Tyrosine Kinase & PTP lists
PEZ-class FERM-PTPs are found in the animal world from flies to vertebrates. These PTPs are suspected to regulate cell adhesion and motility in vertebrates, and are required for proper development in the fly. Other major model organisms such as yeast and C. elegans lack the PEZ-class proteins, and so the fly is the most tractable model system to study Pez function in vivo.
Alignment of D. melanogaster and human Pez proteins. Identities are highlighted black, similarities are boxed and gray. The FERM domain and the PTP domain (defined as the sequence corresponding to PTP1B) are boxed. “Pro motifs” are bracketed and numbered. PTP functional loops are indicated: the equivalent of the WPD motif has a dashed underline; the active site loop is double underlined. See Edwards et al. 2001 for further information.
Recently, phosphosite.org has defined six phosphorylation sites in human and mouse Pez. All six are indicated on the figure as red stars. Remarkably, five of the six phosphorylations lie within the Pro motifs, on conserved residues. This validates our prediction that the Pro motifs are conserved because they are functional protein-protein interaction sites. At a minimum, they are kinase recognition sites; they may also be docking sites for other proteins, and docking would likely be modulated by the phosphorylation state of these residues.
Edwards et al. 2001 aligned the FERM domains from all three classes of FERM-PTPs, and found that there are certain residues that are conserved within a given class, but differ significantly in the other classes. These "class-specific" conserved residues were further analyzed for Pez (above). When these residues (in gray) are plotted on the FERM crystal structure, it can be seen that most of them lie on one face of the protein. We hypothesize that these residues represent the "footprint" of a PEZ-specific ligand.
