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PMID: 1710979 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The SH2 and SH3 domains of pp60src direct stable association with tyrosine phosphorylated proteins p130 and p110.

The EMBO journal ·Vol. 10 ·No. 7 ·1991-07-00 ·Pages 1689-98

Kanner SB, Reynolds AB, Wang HC, Vines RR, Parsons JT

Abstract

Transformation of chicken embryo cells with the tyrosine kinase oncogene src results in the tyrosine phosphorylation of numerous cellular proteins. We have recently generated monoclonal antibodies to individual tyrosine phosphorylated cellular src substrates, several of which are directed to the phosphotyrosine-containing proteins p130 and p110. These proteins form stable complexes with activated variants of pp60src. Mutagenesis of the src homology domains (SH2 and SH3) of activated pp60src resulted in src variants with altered association with p130 and p110. Analysis of these variants showed that the SH3 domain was required for association of p110, while the SH2 domain contained residues necessary for the formation of the ternary complex involving p130, p110 and pp60src. Both the tyrosine phosphorylation status and pp60src association of p130 and p110 appeared to correlate, in part, with the extent of cell transformation. Biochemical analysis demonstrated that p130 and p110 were substrates of both serine/threonine and tyrosine kinases. In addition, p130 was redistributed from the nucleus to cellular membranes upon src transformation, whereas p110, which normally colocalized with cytoskeletal elements, was observed in adhesion plaques (podosomes) in src transformed cells. These data indicate that tyrosine phosphorylation of two different phosphoproteins may play a role during src transformation either by directing their interaction with pp60src, by redirecting subcellular distribution or both.

MeSH Terms
Animals Antibodies, Monoclonal/immunology Chick Embryo Mutagenesis Peptide Mapping Phosphoproteins/chemistry Phosphorylation Phosphotyrosine Protein Conformation Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins pp60(c-src)/chemistry,genetics,immunology Sequence Homology, Nucleic Acid Serine/metabolism Structure-Activity Relationship Subcellular Fractions/chemistry Threonine/metabolism Tyrosine/analogs & derivatives,chemistry,metabolism
Chemicals
Antibodies, Monoclonal Phosphoproteins Phosphotyrosine Threonine Tyrosine Serine Protein-Tyrosine Kinases Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kanner S B
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Reynolds A B
Wang H C
Vines R R
Parsons J T
References (62)
62 references, click to expand
  1. Transformation by pp60src or stimulation of cells with epidermal growth factor induces the stable association of tyrosine-phosphorylated cellular proteins with GTPase-activating protein.
    Mol Cell Biol. 1991 Feb;11(2):945-53 PMID: 1703633
  2. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation.
    Cell. 1987 Apr 10;49(1):65-73 PMID: 3103925
  3. Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors.
    Science. 1990 Nov 16;250(4983):979-82 PMID: 2173144
  4. Src homology region 2 domains direct protein-protein interactions in signal transduction.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8622-6 PMID: 2236073
  5. Mutations in src homology regions 2 and 3 of activated chicken c-src that result in preferential transformation of mouse or chicken cells.
    Proc Natl Acad Sci U S A. 1990 Nov;87(21):8592-6 PMID: 1700434
  6. Evidence that a phosphotyrosine-containing 120,000 Da protein from Rous sarcoma virus-infected cells is phosphorylated by pp60v-src.
    Oncogene Res. 1989;4(3):185-94 PMID: 2472591
  7. Direct activation of the serine/threonine kinase activity of Raf-1 through tyrosine phosphorylation by the PDGF beta-receptor.
    Cell. 1989 Aug 25;58(4):649-57 PMID: 2475255
  8. Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins.
    Cell. 1989 Sep 22;58(6):1121-33 PMID: 2550144
  9. Stable association of activated pp60src with two tyrosine-phosphorylated cellular proteins.
    Mol Cell Biol. 1989 Sep;9(9):3951-8 PMID: 2476666
  10. Platelet-derived growth factor (PDGF) binding promotes physical association of PDGF receptor with phospholipase C.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8232-6 PMID: 2554305
  11. PDGF induction of tyrosine phosphorylation of GTPase activating protein.
    Nature. 1989 Dec 7;342(6250):711-4 PMID: 2480526
  12. Linker insertion-deletion mutagenesis of the v-src gene: isolation of host- and temperature-dependent mutants.
    J Virol. 1989 Feb;63(2):542-54 PMID: 2536090
  13. Src homology 2 domain deletion mutants of p60v-src do not phosphorylate cellular proteins of 120-150 kDa.
    Oncogene. 1989 Feb;4(2):231-6 PMID: 2494631
  14. A mutation in v-src that removes a single conserved residue in the SH-2 domain of pp60v-src restricts transformation in a host-dependent manner.
    J Virol. 1989 Jan;63(1):338-48 PMID: 2462061
  15. Deletions and insertions within an amino-terminal domain of pp60v-src inactivate transformation and modulate membrane stability.
    J Virol. 1989 Jan;63(1):291-302 PMID: 2535735
  16. Epidermal growth factor stimulates tyrosine phosphorylation of phospholipase C-II independently of receptor internalization and extracellular calcium.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1568-72 PMID: 2466293
  17. Genetics of src: structure and functional organization of a protein tyrosine kinase.
    Curr Top Microbiol Immunol. 1989;147:79-127 PMID: 2482802
  18. Activation of the oncogenic potential of the avian cellular src protein by specific structural alteration of the carboxy terminus.
    EMBO J. 1987 Aug;6(8):2359-64 PMID: 2822389
  19. Structural features of the carboxy terminus of p60c-src that are required for the regulation of its intrinsic kinase activity.
    Jpn J Cancer Res. 1987 Dec;78(12):1354-62 PMID: 3123438
  20. Tyrosine phosphorylations in vivo associated with v-fms transformation.
    Mol Cell Biol. 1988 Jan;8(1):176-85 PMID: 2447483
  21. Nonmyristoylated p60v-src fails to phosphorylate proteins of 115-120 kDa in chicken embryo fibroblasts.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2608-12 PMID: 2451829
  22. Phosphotyrosine-containing 120,000-dalton protein coimmunoprecipitated with pp60v-src from Rous sarcoma virus-transformed mammalian cells.
    Virology. 1986 May;151(1):86-99 PMID: 2421483
  23. Sequence similarity of phospholipase C with the non-catalytic region of src.
    Nature. 1988 Mar 17;332(6161):269-72 PMID: 2831461
  24. Non-catalytic domains of cytoplasmic protein-tyrosine kinases: regulatory elements in signal transduction.
    Oncogene. 1988 Nov;3(5):491-5 PMID: 3078956
  25. Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton.
    J Cell Biol. 1989 Jun;108(6):2401-8 PMID: 2472406
  26. Novel tyrosine phosphorylations accompany the activation of pp60c-src during chemical carcinogenesis.
    Oncogene. 1989 Mar;4(3):295-300 PMID: 2468123
  27. Activation of pp60c-src transforming potential by mutations altering the structure of an amino terminal domain containing residues 90-95.
    Oncogene Res. 1988;3(4):343-55 PMID: 2465527
  28. Immunoaffinity purification of tyrosine-phosphorylated cellular proteins.
    J Immunol Methods. 1989 Jun 2;120(1):115-24 PMID: 2471744
  29. Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene.
    Mol Cell Biol. 1989 Feb;9(2):629-38 PMID: 2469003
  30. Thrombin treatment induces rapid changes in tyrosine phosphorylation in platelets.
    Proc Natl Acad Sci U S A. 1989 Feb;86(3):901-5 PMID: 2464830
  31. Platelet tyrosine-specific protein phosphorylation is regulated by thrombin.
    Mol Cell Biol. 1988 Sep;8(9):3603-10 PMID: 2464741
  32. Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies.
    Mol Cell Biol. 1988 Aug;8(8):3035-42 PMID: 2463469
  33. Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrate.
    Nature. 1988 Dec 22-29;336(6201):738-44 PMID: 2462672
  34. Monoclonal antibodies to phosphotyrosine.
    J Immunol Methods. 1988 May 9;109(2):277-85 PMID: 2452204
  35. Activation of pp60c-src tyrosine kinase specific activity in tumor-derived Syrian hamster embryo cells.
    Oncogene. 1988 Apr;2(4):327-35 PMID: 2452399
  36. Identification of multiple novel polypeptide substrates of the v-src, v-yes, v-fps, v-ros, and v-erb-B oncogenic tyrosine protein kinases utilizing antisera against phosphotyrosine.
    Oncogene. 1988 Apr;2(4):305-15 PMID: 2452398
  37. A novel viral oncogene with structural similarity to phospholipase C.
    Nature. 1988 Mar 17;332(6161):272-5 PMID: 2450282
  38. Cell transformation by the viral src oncogene.
    Annu Rev Cell Biol. 1987;3:31-56 PMID: 2446642
  39. Tyrosine-specific protein phosphorylation is regulated by glycoprotein IIb-IIIa in platelets.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2234-8 PMID: 2928328
  40. Oligonucleotide-directed mutagenesis: a simple method using two oligonucleotide primers and a single-stranded DNA template.
    DNA. 1984 Dec;3(6):479-88 PMID: 6096101
  41. Protein tyrosine phosphorylation in the cell cycle of BALB/c 3T3 fibroblasts.
    Proc Natl Acad Sci U S A. 1986 Nov;83(21):8191-5 PMID: 3464948
  42. PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex.
    Cell. 1990 Apr 6;61(1):125-33 PMID: 2156626
  43. Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases.
    Proc Natl Acad Sci U S A. 1990 May;87(9):3328-32 PMID: 2110361
  44. Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases.
    Nature. 1990 Jan 25;343(6256):377-81 PMID: 1689011
  45. Tyrosine kinase activity is essential for the association of phospholipase C-gamma with the epidermal growth factor receptor.
    Mol Cell Biol. 1990 Feb;10(2):435-41 PMID: 2153914
  46. Binding of GAP to activated PDGF receptors.
    Science. 1990 Mar 30;247(4950):1578-81 PMID: 2157284
  47. Signal transduction by receptors with tyrosine kinase activity.
    Cell. 1990 Apr 20;61(2):203-12 PMID: 2158859
  48. Activation of the proto-oncogene p60c-src by point mutations in the SH2 domain.
    Mol Cell Biol. 1990 Jun;10(6):2855-62 PMID: 2111444
  49. Site-directed mutagenesis of the SH2- and SH3-coding domains of c-src produces varied phenotypes, including oncogenic activation of p60c-src.
    Mol Cell Biol. 1990 Apr;10(4):1307-18 PMID: 2108315
  50. Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex.
    Mol Cell Biol. 1990 May;10(5):2359-66 PMID: 1691440
  51. Binding of transforming protein, P47gag-crk, to a broad range of phosphotyrosine-containing proteins.
    Science. 1990 Jun 22;248(4962):1537-9 PMID: 1694307
  52. Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor.
    Nature. 1990 Jun 28;345(6278):810-3 PMID: 1694265
  53. Association of the v-crk oncogene product with phosphotyrosine-containing proteins and protein kinase activity.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2638-42 PMID: 1690891
  54. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation.
    J Immunol. 1990 Mar 1;144(5):1591-9 PMID: 1689750
  55. A 42-kD tyrosine kinase substrate linked to chromaffin cell secretion exhibits an associated MAP kinase activity and is highly related to a 42-kD mitogen-stimulated protein in fibroblasts.
    J Cell Biol. 1990 Mar;110(3):731-42 PMID: 1689732
  56. Glycoprotein tyrosine phosphorylation in Rous sarcoma virus-transformed chicken embryo fibroblasts.
    Mol Cell Biol. 1990 Feb;10(2):837-41 PMID: 1689002
  57. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin.
    EMBO J. 1990 Jul;9(7):2125-31 PMID: 2357961
  58. Monoclonal antibodies to Rous sarcoma virus pp60src react with enzymatically active cellular pp60src of avian and mammalian origin.
    J Virol. 1984 Aug;51(2):272-82 PMID: 6205164
  59. Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses.
    J Virol. 1983 Nov;48(2):352-60 PMID: 6312092
  60. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain.
    Cell. 1987 Apr 10;49(1):83-91 PMID: 3103927
  61. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src.
    Cell. 1987 Apr 10;49(1):75-82 PMID: 3103926
  62. Tyrosine phosphorylation of a 120-kilodalton pp60src substrate upon epidermal growth factor and platelet-derived growth factor receptor stimulation and in polyomavirus middle-T-antigen-transformed cells.
    Mol Cell Biol. 1991 Feb;11(2):713-20 PMID: 1703631
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-07-00
Pages
1689-98
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452840
Subset
IM
Grants
NCI NIH HHS · CA08316 · United States
NCI NIH HHS · CA29243 · United States
NCI NIH HHS · CA40042 · United States
External Links
PubMed source PMC Full Text View journal details
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