1H, 15N and 13C resonance assignments for the PTB domain of the signaling protein Shc.

Abstract

Protein-protein interaction via phosphotyrosine is anessential mechanism in cell signal transduction (Paw-son and Nash, 2000). One of the key players inorchestrating cell signaling via tyrosine phosphoryla-tion is the phosphotyrosine binding (PTB) domain ofthe signaling protein Shc (Kavanaugh and Williams,1994). The PTB domain of Shc binds in a highlyspecific manner to the cytoplasmic domain of acti-vatedtyrosine-phosphorylatedreceptorsand relaysthesignal to downstream proteins for cellular activitiessuch as cell growth, cell differentiation and apopto-sis. In order to understand the structural basis of theaction of the PTB domain, we have already solveda high resolution solution structure of the Shc PTBdomain complexed to a tyrosine-phosphorylated pep-tide (Zhou et al., 1995). However, the notion thatproteins lack intrinsic globular structure under phys-iological conditions and that the attainment of fullyfolded structure only occurs upon ligand binding israpidly gaining popularity (Dyson and Wright, 2002).It has been argued that such a behavior of proteinsaccounts for their diverse structural and functionalversatility. Giventhat the Shc PTB domainis function-ally promiscuous in its ability to recognize receptorsas diverse as growth factor, antigen, cytokine, andG-protein-coupled and hormone receptors, it is pos-sible that such a mechanism of protein structural andfunctional versatility may also be operative in this im-portant protein module. In an effort to understand theextent to which ligand binding controls the formationof the intrinsic globular fold in the case of the Shc