Differentiation of peptide molecular recognition by phospholipase C gamma-1 Src homology-2 domain and a mutant Tyr phosphatase PTP1bC215S. 1995

D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
Department of Chemistry, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.

Activated epidermal growth factor receptor (EGFR) undergoes autophosphorylation on several cytoplasmic tyrosine residues, which may then associate with the src homology-2 (SH2) domains of effector proteins such as phospholipase C gamma-1 (PLC gamma-1). Specific phosphotyrosine (pTyr)-modified EGFR fragment peptides can inhibit this intermolecular binding between activated EGFR and a tandem amino- and carboxy-terminal (N/C) SH2 protein construct derived from PLC gamma-1. In this study, we further explored the molecular recognition of phosphorylated EGFR988-998 (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly, I) by PLC gamma-1 N/C SH2 in terms of singular Ala substitutions for amino acid residues N- and C-terminal to the pTyr (P site) of phosphopeptide I. Comparison of the extent to which these phosphopeptides inhibited binding of PLC gamma-1 N/C SH2 to activated EGFR showed the critical importance of amino acid side chains at positions P+2 (Ile994), P+3 (Pro995), and P+4 (Gln996). Relative to phosphopeptide I, multiple Ala substitution throughout the N-terminal sequence, N-terminal sequence, N-terminal truncation, or dephosphorylation of pTyr each resulted in significantly decreased binding to PLC gamma-1 N/C SH2. These structure-activity results were analyzed by molecular modeling studies of the predicted binding of phosphopeptide I to each the N- and C-terminal SH2 domains of PLC gamma-1.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
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
D010738 Type C Phospholipases A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS. Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D010748 Phosphopeptides PEPTIDES that incorporate a phosphate group via PHOSPHORYLATION. Phosphopeptide
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
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
D003196 Computer Graphics The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation. Computer Graphic,Graphic, Computer,Graphics, Computer
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
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D016415 Sequence Alignment The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations

Related Publications

D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
March 1998, Biochemical and biophysical research communications,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
February 1998, Journal of immunology (Baltimore, Md. : 1950),
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
July 2013, Molecular bioSystems,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
February 2007, Molecular and cellular biology,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
March 1993, Nature,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
February 1995, The Biochemical journal,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
January 2005, Journal of immunology (Baltimore, Md. : 1950),
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
June 2019, Journal of neuroimmunology,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
August 2017, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
D MacLean, and A M Sefler, and G Zhu, and S J Decker, and A R Saltiel, and J Singh, and D McNamara, and E M Dobrusin, and T K Sawyer
June 2003, Genetics,
Copied contents to your clipboard!