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PMID: 1594631 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions.

Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT

Abstract

Expression of the Rous sarcoma virus-encoded oncoprotein, pp60v-src, subverts the normal regulation of cell growth, which results in oncogenic transformation. This process requires the intrinsic protein-tyrosine kinase activity of pp60v-src and is associated with an increase in tyrosine phosphorylation of a number of cellular proteins, candidate substrates for pp60v-src. We report here the isolation of a cDNA encoding a protein, pp125, that is a major phosphotyrosine-containing protein in untransformed chicken embryo cells and exhibits an increase in phosphotyrosine in pp60v-src-transformed chicken embryo cells. This cDNA encodes a cytoplasmic protein-tyrosine kinase which, based upon its predicted amino acid sequence and structure, is the prototype for an additional family of protein-tyrosine kinases. Immunofluorescence localization experiments show that pp125 is localized to focal adhesions; hence, we suggest the name focal adhesion kinase.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Adhesion Cell Adhesion Molecules/genetics,metabolism Cell Transformation, Viral Chick Embryo Cloning, Molecular Cytoskeletal Proteins/metabolism DNA/genetics Fluorescent Antibody Technique Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Microfilament Proteins Molecular Sequence Data Molecular Weight Phosphoproteins/genetics Protein-Tyrosine Kinases/genetics,metabolism Restriction Mapping Sequence Alignment Tensins
Chemicals
Cell Adhesion Molecules Cytoskeletal Proteins Microfilament Proteins Phosphoproteins Tensins DNA Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schaller M D
Department of Microbiology, School of Medicine, University of Virginia, Charlottesville 22908.
Borgman C A
Cobb B S
Vines R R
Reynolds A B
Parsons J T
References (34)
34 references, click to expand
  1. 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
  2. Regulation of tyrosine phosphorylation of the nicotinic acetylcholine receptor at the rat neuromuscular junction.
    Neuron. 1990 Mar;4(3):367-78 PMID: 1690564
  3. Amino acid alterations within a highly conserved region of the Rous sarcoma virus src gene product pp60src inactivate tyrosine protein kinase activity.
    Mol Cell Biol. 1984 May;4(5):862-6 PMID: 6328273
  4. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  5. A simple method for displaying the hydropathic character of a protein.
    J Mol Biol. 1982 May 5;157(1):105-32 PMID: 7108955
  6. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  7. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  8. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.
    Science. 1991 May 3;252(5006):668-74 PMID: 1708916
  9. Identification and characterization of a novel cytoskeleton-associated pp60src substrate.
    Mol Cell Biol. 1991 Oct;11(10):5113-24 PMID: 1922035
  10. Oncogenes and signal transduction.
    Cell. 1991 Jan 25;64(2):281-302 PMID: 1846320
  11. Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein.
    Cell Regul. 1991 Nov;2(11):951-64 PMID: 1725602
  12. Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins.
    Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8392-6 PMID: 1717976
  13. Presence of an SH2 domain in the actin-binding protein tensin.
    Science. 1991 May 3;252(5006):712-5 PMID: 1708917
  14. T cell antigen receptor activation pathways: the tyrosine kinase connection.
    Cell. 1991 Mar 8;64(5):875-8 PMID: 1848158
  15. Protein tyrosine phosphorylation and the adhesive functions of platelets.
    Curr Opin Cell Biol. 1991 Oct;3(5):869-79 PMID: 1931088
  16. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
    Science. 1991 Jul 26;253(5018):407-14 PMID: 1862342
  17. High-expression vectors with multiple cloning sites for construction of trpE fusion genes: pATH vectors.
    Methods Enzymol. 1991;194:477-90 PMID: 2005804
  18. Improved tools for biological sequence comparison.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 PMID: 3162770
  19. Genetics of src: structure and functional organization of a protein tyrosine kinase.
    Curr Top Microbiol Immunol. 1989;147:79-127 PMID: 2482802
  20. Leukocytes express a novel gene encoding a putative transmembrane protein-kinase devoid of an extracellular domain.
    Nature. 1988 Jun 16;333(6174):672-6 PMID: 2836739
  21. Phosphorylation of talin at tyrosine in Rous sarcoma virus-transformed cells.
    Mol Cell Biol. 1987 Jan;7(1):371-8 PMID: 3031468
  22. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton.
    Annu Rev Cell Biol. 1988;4:487-525 PMID: 3058164
  23. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.
    Science. 1988 Jul 1;241(4861):42-52 PMID: 3291115
  24. Immunoaffinity purification of tyrosine-phosphorylated cellular proteins.
    J Immunol Methods. 1989 Jun 2;120(1):115-24 PMID: 2471744
  25. 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
  26. Catalytic and non-catalytic domains of the Fujinami sarcoma virus P130gag-fps protein-tyrosine kinase distinguished by the expression of v-fps polypeptides in Escherichia coli.
    Oncogene. 1987 May;1(2):181-91 PMID: 2449646
  27. Cell transformation by the viral src oncogene.
    Annu Rev Cell Biol. 1987;3:31-56 PMID: 2446642
  28. Functional analysis of point mutations in the AAUAAA motif of the SV40 late polyadenylation signal.
    Nucleic Acids Res. 1989 May 25;17(10):3899-908 PMID: 2543957
  29. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  30. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.
    Cell. 1986 Jan 31;44(2):283-92 PMID: 3943125
  31. The ltk receptor tyrosine kinase is expressed in pre-B lymphocytes and cerebral neurons and uses a non-AUG translational initiator.
    EMBO J. 1990 Jul;9(7):2279-87 PMID: 2357970
  32. 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
  33. Signal transduction by receptors with tyrosine kinase activity.
    Cell. 1990 Apr 20;61(2):203-12 PMID: 2158859
  34. Paxillin: a new vinculin-binding protein present in focal adhesions.
    J Cell Biol. 1990 Sep;111(3):1059-68 PMID: 2118142
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1992-06-01
Pages
5192-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49256
Subset
IM
Grants
NCI NIH HHS · CA29243 · United States
NCI NIH HHS · CA40042 · United States
Databases
GENBANK
M86656
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