Structural highlights
Function
[FRS3_HUMAN] Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion oncoprotein, formed by the t(2;5) chromosomal translocation in anaplastic large-cell lymphomas, has constitutive tyrosine kinase activity and interacts with a number of signaling molecules. One of the interacting partners of NPM-ALK is the adaptor protein, Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT), and mutations that deprive NPM-ALK of all three of the SNT-binding sites significantly reduced the transforming activity. In this study, the interactions of the three binding sites in NPM-ALK with the phosphotyrosine binding (PTB) domain of SNT-2 were analyzed. First, by isothermal titration calorimetry, we found that the phosphorylation-independent binding site in NPM-ALK interacts with the SNT-2 PTB domain more tightly than the phosphorylation-dependent binding sites. Second, the solution structure of the SNT-2 PTB domain in complex with the nonphosphorylated NPM-ALK peptide was determined by nuclear magnetic resonance spectroscopy. The NPM-ALK peptide interacts with the hydrophobic surface of the PTB domain and intermolecularly extends the PTB beta-sheet. This interaction mode is much broader and more extensive than those of the phosphorylation-dependent binding sites. Our results indicate that the higher binding activity of the phosphorylation-independent binding site is caused by additional hydrophobic interactions.
Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2.,Koshiba S, Li H, Motoda Y, Tomizawa T, Kasai T, Tochio N, Yabuki T, Harada T, Watanabe S, Tanaka A, Shirouzu M, Kigawa T, Yamamoto T, Yokoyama S J Struct Funct Genomics. 2010 May 8. PMID:20454865[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gotoh N, Laks S, Nakashima M, Lax I, Schlessinger J. FRS2 family docking proteins with overlapping roles in activation of MAP kinase have distinct spatial-temporal patterns of expression of their transcripts. FEBS Lett. 2004 Apr 23;564(1-2):14-8. PMID:15094036 doi:10.1016/S0014-5793(04)00287-X
- ↑ Koshiba S, Li H, Motoda Y, Tomizawa T, Kasai T, Tochio N, Yabuki T, Harada T, Watanabe S, Tanaka A, Shirouzu M, Kigawa T, Yamamoto T, Yokoyama S. Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2. J Struct Funct Genomics. 2010 May 8. PMID:20454865 doi:10.1007/s10969-010-9091-x
