Home LiteratureArticle Details
PMID: 7579684 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Paxillin, a tyrosine phosphorylated focal adhesion-associated protein binds to the carboxyl terminal domain of focal adhesion kinase.

Molecular biology of the cell ·Vol. 6 ·No. 6 ·1995-06-00 ·Pages 637-47

Hildebrand JD, Schaller MD, Parsons JT

Abstract

Focal adhesion kinase (pp125FAK or FAK) and paxillin colocalize with integrins in structures called focal adhesions. pp125FAK plays an important role in the transmission of integrin-induced cytoplasmic signals. Paxillin has also been implicated in cell signaling by virtue of its association with the protein tyrosine kinases pp60src and Csk (C-terminal Src kinase) as well as with the adapter/oncoprotein p47gag-crk. In this report we show that endogenous pp125FAK and paxillin form a stable complex both in vivo and in vitro and that this interaction is direct, requiring only pp125FAK and paxillin. The paxillin binding site on pp125FAK has been localized to the carboxy-terminal 148 residues of pp125FAK, but appears to be distinct from the previously identified focal adhesion-targeting sequence also present in the carboxy-terminal domain of pp125FAK. The interaction of paxillin and pp125FAK is independent of the adhesion of cells to the extracellular matrix, as the association can be detected in suspension cells as well as those attached to fibronectin.

Related Genes
FAK GST
MeSH Terms
Animals Base Sequence Blotting, Western Cell Adhesion Cell Adhesion Molecules/immunology,metabolism Cells, Cultured Chick Embryo Cytoskeletal Proteins/metabolism Epitopes/immunology Extracellular Matrix/metabolism Fluorescent Antibody Technique Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gene Expression Regulation, Viral Genetic Vectors Glutathione Transferase/genetics,metabolism Molecular Sequence Data Paxillin Phosphoproteins/metabolism Precipitin Tests Protein Binding Protein-Tyrosine Kinases/immunology,metabolism Receptor, Insulin/immunology,metabolism Recombinant Fusion Proteins/immunology,metabolism Sequence Deletion Structure-Activity Relationship
Chemicals
Cell Adhesion Molecules Cytoskeletal Proteins Epitopes Paxillin Phosphoproteins Recombinant Fusion Proteins Glutathione Transferase Protein-Tyrosine Kinases Receptor, Insulin Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hildebrand J D
Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
Schaller M D
Parsons J T
References (40)
40 references, click to expand
  1. Identification and characterization of a high-affinity interaction between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts.
    Mol Cell Biol. 1993 Aug;13(8):4648-56 PMID: 7687742
  2. 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
  3. Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions.
    J Cell Biol. 1993 Nov;123(4):993-1005 PMID: 8227154
  4. Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK.
    Mol Cell Biol. 1993 Feb;13(2):785-91 PMID: 8423801
  5. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  6. Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response and cross-talk with bombesin.
    J Biol Chem. 1994 Jan 7;269(1):704-10 PMID: 8276872
  7. Monoclonal antibodies specific for the carboxy terminus of simian virus 40 large T antigen.
    J Virol. 1984 Nov;52(2):483-91 PMID: 6208378
  8. Detection of Src homology 3-binding proteins, including paxillin, in normal and v-Src-transformed Balb/c 3T3 cells.
    J Biol Chem. 1993 Jul 15;268(20):14956-63 PMID: 8325872
  9. Transmembrane molecular assemblies in cell-extracellular matrix interactions.
    Curr Opin Cell Biol. 1991 Oct;3(5):849-53 PMID: 1931085
  10. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly.
    J Cell Biol. 1992 Nov;119(4):893-903 PMID: 1385444
  11. Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase.
    J Biol Chem. 1992 Nov 25;267(33):23439-42 PMID: 1429685
  12. Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src.
    Mol Cell Biol. 1994 Mar;14(3):1680-8 PMID: 7509446
  13. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192-6 PMID: 1594631
  14. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation.
    Nature. 1992 Aug 20;358(6388):690-2 PMID: 1379699
  15. The LIM domain is a modular protein-binding interface.
    Cell. 1994 Oct 21;79(2):211-9 PMID: 7954790
  16. Tyrosine phosphorylation of the focal adhesion kinase pp125FAK during development: relation to paxillin.
    J Cell Sci. 1993 Jul;105 ( Pt 3):637-45 PMID: 8408291
  17. Bombesin stimulation of p125 focal adhesion kinase tyrosine phosphorylation. Role of protein kinase C, Ca2+ mobilization, and the actin cytoskeleton.
    J Biol Chem. 1993 Jul 5;268(19):14261-8 PMID: 8314789
  18. Analysis of the binding of the Src homology 2 domain of Csk to tyrosine-phosphorylated proteins in the suppression and mitotic activation of c-Src.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3984-8 PMID: 7513429
  19. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties.
    Cell. 1992 Jul 24;70(2):351-64 PMID: 1638635
  20. Primary sequence of paxillin contains putative SH2 and SH3 domain binding motifs and multiple LIM domains: identification of a vinculin and pp125Fak-binding region.
    J Cell Sci. 1994 Jun;107 ( Pt 6):1583-91 PMID: 7525621
  21. 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
  22. Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK.
    Mol Cell Biol. 1994 Jan;14(1):147-55 PMID: 7505391
  23. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin.
    Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8487-91 PMID: 1528852
  24. 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
  25. Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein.
    Cell Regul. 1991 Nov;2(11):951-64 PMID: 1725602
  26. Lysophosphatidic acid stimulates tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130. Signaling pathways and cross-talk with platelet-derived growth factor.
    J Biol Chem. 1994 Mar 25;269(12):9345-51 PMID: 7510708
  27. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton.
    Annu Rev Cell Biol. 1988;4:487-525 PMID: 3058164
  28. SH2 domains recognize specific phosphopeptide sequences.
    Cell. 1993 Mar 12;72(5):767-78 PMID: 7680959
  29. Integrins and other cell adhesion molecules.
    FASEB J. 1990 Aug;4(11):2868-80 PMID: 2199285
  30. Bombesin, vasopressin, and endothelin rapidly stimulate tyrosine phosphorylation of the focal adhesion-associated protein paxillin in Swiss 3T3 cells.
    J Biol Chem. 1993 Oct 15;268(29):22060-5 PMID: 8408063
  31. Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets.
    J Cell Biol. 1992 Nov;119(4):905-12 PMID: 1385445
  32. Identification and characterization of a novel cytoskeleton-associated pp60src substrate.
    Mol Cell Biol. 1991 Oct;11(10):5113-24 PMID: 1922035
  33. Integrins: versatility, modulation, and signaling in cell adhesion.
    Cell. 1992 Apr 3;69(1):11-25 PMID: 1555235
  34. Transmembrane signalling by integrins.
    Trends Cell Biol. 1992 Oct;2(10):304-8 PMID: 14731926
  35. Immunoaffinity purification of tyrosine-phosphorylated cellular proteins.
    J Immunol Methods. 1989 Jun 2;120(1):115-24 PMID: 2471744
  36. pp125FAK-dependent tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk.
    Mol Cell Biol. 1995 May;15(5):2635-45 PMID: 7537852
  37. Paxillin: a new vinculin-binding protein present in focal adhesions.
    J Cell Biol. 1990 Sep;111(3):1059-68 PMID: 2118142
  38. Signal transduction from the extracellular matrix.
    J Cell Biol. 1993 Feb;120(3):577-85 PMID: 8381117
  39. Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors.
    J Virol. 1987 Oct;61(10):3004-12 PMID: 3041020
  40. ADP-ribosylation of rho p21 inhibits lysophosphatidic acid-induced protein tyrosine phosphorylation and phosphatidylinositol 3-kinase activation in cultured Swiss 3T3 cells.
    J Biol Chem. 1993 Nov 25;268(33):24535-8 PMID: 8227009
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.6.6.637
Published
1995-06-00
Pages
637-47
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC301225
Subset
IM
Grants
NCI NIH HHS · CA-29243 · United States
NCI NIH HHS · CA-40042 · United States
NCI NIH HHS · CA-60697 · United States
Databases
GENBANK
M86656
External Links
PubMed source DOI: 10.1091/mbc.6.6.637 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2