BIOMAT Database Logo BIOMAT Database Logo

Phosphatidylinositol 3-kinase p85 SH2 domain specificity defined by direct phosphopeptide/SH2 domain binding. 1993

E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.

We have developed a competition binding assay to quantify relative affinities of isolated Src-homology 2 (SH2) domains for phosphopeptide sequences. Eleven synthetic 11-12-amino acid phosphopeptides containing YMXM or YVXM recognition motifs bound to a PI 3-kinase p85 SH2 domain with highest affinities, including sequences surrounding phosphorylated tyrosines of the PDGF, CSF-1/c-Fms, and kit-encoded receptors, IRS-1, and polyoma middle T antigens; matched, unphosphorylated sequences did not bind. A scrambled YMXM phosphopeptide or sequences corresponding to the GAP or PLC-gamma SH2 domain binding motifs of the PDGF, FGF, and EGF receptors bound to the p85 SH2 domain with 30-100-fold reduced affinity, indicating that this affinity range confers specificity. Binding specificity was appropriately reversed with an SH2 domain from PLC-gamma: a phosphopeptide corresponding to the site surrounding PDGF receptor Tyr1021 binds with approximately 40-fold higher affinity than a YMXM-phosphopeptide. We conclude that essential features of specific phosphoprotein/SH2 domain interactions can be reconstituted using truncated versions of both the phosphoprotein (a phosphopeptide) and cognate SH2 domain-containing protein (the SH2 domain). SH2 domain binding specificity results from differences in affinity conferred by the linear sequence surrounding phosphotyrosine.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D010750 Phosphoproteins Phosphoprotein
D010770 Phosphotransferases A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7. Kinases,Phosphotransferase,Phosphotransferases, ATP,Transphosphorylase,Transphosphorylases,Kinase,ATP Phosphotransferases
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D019869 Phosphatidylinositol 3-Kinases Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell. PI-3 Kinase,Phosphatidylinositol-3-OH Kinase,PtdIns 3-Kinase,PI 3-Kinase,PI-3K,PI3 Kinases,PI3-Kinase,Phosphoinositide 3 Kinases,Phosphoinositide 3-Hydroxykinase,PtdIns 3-Kinases,3-Hydroxykinase, Phosphoinositide,Kinase, PI-3,Kinase, Phosphatidylinositol-3-OH,Kinases, PI3,Kinases, Phosphoinositide 3,PI 3 Kinase,PI3 Kinase,Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 OH Kinase,Phosphoinositide 3 Hydroxykinase,PtdIns 3 Kinase,PtdIns 3 Kinases

Related Publications

E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Cyclic peptide inhibitors of phosphatidylinositol 3-kinase p85 SH2 domain binding.
June 1994, Biochemical and biophysical research communications,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes.
April 1996, Nature structural biology,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Structure of an SH2 domain of the p85 alpha subunit of phosphatidylinositol-3-OH kinase.
August 1992, Nature,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Phosphopeptide binding to the N-terminal SH2 domain of the p85 alpha subunit of PI 3'-kinase: a heteronuclear NMR study.
July 1994, Protein science : a publication of the Protein Society,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Genetic analysis of a phosphatidylinositol 3-kinase SH2 domain reveals determinants of specificity.
September 1994, Molecular and cellular biology,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.
March 1992, Molecular and cellular biology,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
SH2 domain specificity determination using oriented phosphopeptide library.
January 1995, Methods in enzymology,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase.
March 2010, Proceedings of the National Academy of Sciences of the United States of America,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
The C-terminal SH2 domain of p85 accounts for the high affinity and specificity of the binding of phosphatidylinositol 3-kinase to phosphorylated platelet-derived growth factor beta receptor.
April 1992, Molecular and cellular biology,
E Piccione, and R D Case, and S M Domchek, and P Hu, and M Chaudhuri, and J M Backer, and J Schlessinger, and S E Shoelson
An investigation of phosphopeptide binding to SH2 domain.
June 2003, Biochemical and biophysical research communications,
Copied contents to your clipboard!