Structure and function of SH2 domains

SUMMARY In order for cells to respond to their environment, a series of regulated molecular events has to take place. External signalling molecules bind to cellular receptors and thereby trigger the activation of multiple intracellular pathways, which modify cellular phenotypes. The cell-surface receptors for a wide range of polypeptide hormones possess protein tyrosine kinase activity, which is induced by binding of the appropriate extracellular ligand. Tyrosine phosphorylation can act as a molecular switch, by initiating the recruitment of cytoplasmic effector molecules containing Src homology (SH) 2 domains, to activated receptors. These SH2-containing proteins, in turn, regulate intracellular signalling pathways. Here, we discuss the role of tyrosine phosphorylation in triggering signalling pathways, as well as the functions of SH2 domains, which mediate these events through phosphotyrosine-dependent protein-protein interactions.

[1]  L. Cantley,et al.  Oncogenes and signal transduction , 1991, Cell.

[2]  D. Bar-Sagi,et al.  Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras , 1993, Nature.

[3]  T. Pawson,et al.  Non-catalytic domains of cytoplasmic protein-tyrosine kinases: regulatory elements in signal transduction. , 1988, Oncogene.

[4]  J. Bishop,et al.  Torso, a receptor tyrosine kinase required for embryonic pattern formation, shares substrates with the sevenless and EGF-R pathways in Drosophila. , 1993, Genes & development.

[5]  T. Pawson,et al.  Interactions of phosphatidylinositol kinase, GTPase-activating protein (GAP), and GAP-associated proteins with the colony-stimulating factor 1 receptor , 1990, Molecular and cellular biology.

[6]  T. Pawson,et al.  SH2 and SH3 domains: From structure to function , 1992, Cell.

[7]  D. Baltimore,et al.  The noncatalytic src homology region 2 segment of abl tyrosine kinase binds to tyrosine-phosphorylated cellular proteins with high affinity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  D. Baltimore,et al.  Identification of a protein that binds to the SH3 region of Abl and is similar to Bcr and GAP-rho. , 1992, Science.

[9]  Nanxin Li,et al.  Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling , 1993, Nature.

[10]  J. Kuriyan,et al.  Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase. , 1994, Structure.

[11]  T. Hunter,et al.  Phospholipase C-γ is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro , 1989, Cell.

[12]  S. Coughlin,et al.  Role of phosphatidylinositol kinase in PDGF receptor signal transduction. , 1989, Science.

[13]  E. Lapetina,et al.  Association of phosphorylated insulin-like growth factor-I receptor with the SH2 domains of phosphatidylinositol 3-kinase p85. , 1992, The Journal of biological chemistry.

[14]  T. Pawson,et al.  The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1 , 1993, Nature.

[15]  Tony Pawson,et al.  SH2 domain specificity and activity modified by a single residue , 1994, Nature.

[16]  T. Hunter,et al.  Mutation of Tyr697, a GRB2‐binding site, and Tyr721, a PI 3‐kinase binding site, abrogates signal transduction by the murine CSF‐1 receptor expressed in Rat‐2 fibroblasts. , 1993, The EMBO journal.

[17]  T. Pawson,et al.  The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Panayotou,et al.  Interaction of the p85 subunit of PI 3‐kinase and its N‐terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes. , 1992, The EMBO journal.

[19]  A. Ullrich,et al.  The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling , 1992, Cell.

[20]  T Pawson,et al.  SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. , 1991, Science.

[21]  Paul W. Sternberg,et al.  Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva , 1991, Nature.

[22]  T. Fleming,et al.  PDGF induction of tyrosine phosphorylation of GTPase activating protein , 1989, Nature.

[23]  L. Cantley,et al.  Polyoma virus middle T antigen-pp60c-src complex associates with purified phosphatidylinositol 3-kinase in vitro. , 1992, The Journal of biological chemistry.

[24]  J. Downing,et al.  Phospholipase C‐gamma, a substrate for PDGF receptor kinase, is not phosphorylated on tyrosine during the mitogenic response to CSF‐1. , 1989, The EMBO journal.

[25]  B. Mayer,et al.  Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins. , 1990, Science.

[26]  M. Moran,et al.  Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors. , 1990, Science.

[27]  B. Shilo,et al.  The Drosophila EGF receptor homolog (DER) gene is allelic to faint little ball, a locus essential for embryonic development , 1989, Cell.

[28]  S. Harrison,et al.  Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck , 1993, Nature.

[29]  I. Campbell,et al.  Structure of an SH2 domain of the p85α subunit of phosphatidylinositol-3-OH kinase , 1994, Nature.

[30]  B. Mayer,et al.  Mutagenic analysis of the v-crk oncogene: requirement for SH2 and SH3 domains and correlation between increased cellular phosphotyrosine and transformation , 1990, Journal of virology.

[31]  R. Lehmann,et al.  Determination of anteroposterior polarity in Drosophila. , 1987, Science.

[32]  A. Reith,et al.  SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors , 1992, Molecular and cellular biology.

[33]  T. Hunter,et al.  Receptor protein-tyrosine kinases and their signal transduction pathways. , 1994, Annual review of cell biology.

[34]  P. Sternberg,et al.  Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction. , 1991, Genetics.

[35]  M. Jaye,et al.  A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1 , 1991, Molecular and cellular biology.

[36]  C. Turck,et al.  A phosphatidylinositol-3 kinase binds to platelet-derived growth factor receptors through a specific receptor sequence containing phosphotyrosine , 1991, Molecular and cellular biology.

[37]  J. Parsons,et al.  Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK , 1994, Molecular and cellular biology.

[38]  E. Hafen,et al.  A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos , 1993, Cell.

[39]  C. Heldin,et al.  Identification of two juxtamembrane autophosphorylation sites in the PDGF beta‐receptor; involvement in the interaction with Src family tyrosine kinases. , 1993, The EMBO journal.

[40]  M. White,et al.  Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[41]  T. Schüpbach,et al.  The maternal ventralizing locus torpedo is allelic to faint little ball, an embryonic lethal, and encodes the Drosophila EGF receptor homolog , 1989, Cell.

[42]  G. Rubin,et al.  An SH3-SH2-SH3 protein is required for p21 Ras1 activation and binds to sevenless and Sos proteins in vitro , 1993, Cell.

[43]  T. Pawson,et al.  The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp. , 1993, The Journal of biological chemistry.

[44]  Jonathan A. Cooper,et al.  Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo. , 1992, The EMBO journal.

[45]  H. Horvitz,et al.  A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans , 1987, Nature.

[46]  A. Ullrich,et al.  SH2 domains prevent tyrosine dephosphorylation of the EGF receptor: identification of Tyr992 as the high‐affinity binding site for SH2 domains of phospholipase C gamma. , 1992, The EMBO journal.

[47]  J. Kuriyan,et al.  Binding of a high affinity phosphotyrosyl peptide to the Src SH2 domain: Crystal structures of the complexed and peptide-free forms , 1993, Cell.

[48]  G. Rubin,et al.  Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase , 1991, Cell.

[49]  A. Ullrich,et al.  Growth factor receptor tyrosine kinases. , 1988, Annual review of biochemistry.

[50]  T. Pawson,et al.  SH2 domains recognize specific phosphopeptide sequences , 1993, Cell.

[51]  S. Shoelson,et al.  A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding. , 1993, The Journal of biological chemistry.

[52]  R. Weinberg,et al.  Association between GTPase activators for Rho and Ras families , 1992, Nature.

[53]  Jonathan A. Cooper,et al.  GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit , 1992, Molecular and cellular biology.

[54]  T. Pawson,et al.  The association of insulin-elicited phosphotyrosine proteins with src homology 2 domains. , 1992, The Journal of biological chemistry.

[55]  Jonathan A. Cooper,et al.  Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins , 1989, Cell.

[56]  D. Baltimore,et al.  Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo , 1992, Molecular and cellular biology.

[57]  T. Pawson,et al.  Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. , 1990, Trends in genetics : TIG.

[58]  M. Moran,et al.  Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62 , 1992, Cell.

[59]  B. Margolis,et al.  Phosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation. , 1992, The EMBO journal.

[60]  Joseph Schlessinger,et al.  Signal transduction by receptors with tyrosine kinase activity , 1990, Cell.

[61]  H. Horvitz,et al.  C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains , 1992, Nature.

[62]  A. Reith,et al.  W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit receptor. , 1990, Genes & development.

[63]  P Cicchetti,et al.  Identification of a ten-amino acid proline-rich SH3 binding site. , 1993, Science.

[64]  J. Parsons,et al.  pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[65]  S. Courtneidge,et al.  Association between the PDGF receptor and members of the src family of tyrosine kinases , 1990, Cell.

[66]  T. Pawson,et al.  Tyr721 regulates specific binding of the CSF‐1 receptor kinase insert to PI 3′‐kinase SH2 domains: a model for SH2‐mediated receptor‐target interactions. , 1992, The EMBO journal.

[67]  Jonathan A. Cooper,et al.  Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor , 1993, Molecular and cellular biology.

[68]  Julian Downward,et al.  Epidermal growth factor regulates p21 ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor , 1993, Cell.

[69]  D. Baltimore,et al.  Three-dimensional solution structure of the src homology 2 domain of c-abl , 1992, Cell.

[70]  T Pawson,et al.  Src homology region 2 domains direct protein-protein interactions in signal transduction. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[71]  M. White,et al.  IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[72]  T. Pawson,et al.  Identification of residues in GTPase-activating protein Src homology 2 domains that control binding to tyrosine phosphorylated growth factor receptors and p62. , 1992, The Journal of biological chemistry.

[73]  C. Turck,et al.  Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways , 1992, Cell.

[74]  D. Bowtell,et al.  Identification of murine homologues of the Drosophila son of sevenless gene: potential activators of ras. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[75]  E. Russell.  Hereditary anemias of the mouse: a review for geneticists. , 1979, Advances in genetics.

[76]  R. Medema,et al.  Involvement of Shc in insulin- and epidermal growth factor-induced activation of p21ras , 1994, Molecular and cellular biology.

[77]  R. Weinberg,et al.  Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation , 1993, Nature.

[78]  K. Ueki,et al.  Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. , 1993, The Journal of biological chemistry.

[79]  D. Morrison,et al.  Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex , 1990, Molecular and cellular biology.

[80]  R. Weinberg,et al.  Molecular cloning of cDNAs encoding the GAP-associated protein p190: Implications for a signaling pathway from ras to the nucleus , 1992, Cell.

[81]  Jonathan A. Cooper,et al.  Phosphorylation of the PDGF receptor beta subunit creates a tight binding site for phosphatidylinositol 3 kinase. , 1990, The EMBO journal.

[82]  T Pawson,et al.  Interactions between SH2 domains and tyrosine-phosphorylated platelet-derived growth factor beta-receptor sequences: analysis of kinetic parameters by a novel biosensor-based approach , 1993, Molecular and cellular biology.

[83]  T Pawson,et al.  SH2 and SH3 domains , 1993, Current Biology.