Evidence map›Paper›PMID 16000375›Full record

ArticleMolecular biology of the cell2005

Src and FAK kinases cooperate to phosphorylate paxillin kinase linker, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness.

Michael C Brown, Leslie A Cary, Jennifer S Jamieson, Jonathan A Cooper, Christopher E Turner

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 190 citations in OpenAlex.

  1. Review
  2. Review
  3. Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026
    Review
  4. Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026
    Review
  5. Article
  6. Review
  7. Review
  8. Rac1 Suppression by the Focal Adhesion Protein GIT ArfGAP2 and Podocyte Protection.Journal of the American Society of Nephrology : JASN · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. International journal of molecular sciences · 2022
    Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Michael C BrownDepartment of Cell and Developmental Biology, College of Medicine, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Leslie A Cary
Jennifer S Jamieson
Jonathan A Cooper
Christopher E Turner
SUNY Upstate Medical University · USFred Hutch Cancer Center · US

Funding

STRUCTURE AND FUNCTION OF PAXILLINR01GM047607 · NIGMS · UPSTATE MEDICAL UNIVERSITY · PI TURNER, CHRISTOPHER E · 1996 to 2017
$5.5M
SRC FAMILY KINASES AND CELL GROWTH REGULATIONR37CA041072 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A. · 1999 to 2006
$3.3M
SRC FAMILY KINASES AND CELL GROWTH REGULATIONR01CA041072 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI COOPER, JONATHAN A · 1986 to 2011
$2.8M
NCI NIH HHS CA-41072NCI NIH HHS R01 CA041072NCI NIH HHS R37 CA041072NIGMS NIH HHS GM-477607NIGMS NIH HHS R01 GM047607
6 · The paper itself

Abstract

The ArfGAP paxillin kinase linker (PKL)/G protein-coupled receptor kinase-interacting protein (GIT)2 has been implicated in regulating cell spreading and motility through its transient recruitment of the p21-activated kinase (PAK) to focal adhesions. The Nck-PAK-PIX-PKL protein complex is recruited to focal adhesions by paxillin upon integrin engagement and Rac activation. In this report, we identify tyrosine-phosphorylated PKL as a protein that associates with the SH3-SH2 adaptor Nck, in a Src-dependent manner, after cell adhesion to fibronectin. Both cell adhesion and Rac activation stimulated PKL tyrosine phosphorylation. PKL is phosphorylated on tyrosine residues 286/392/592 by Src and/or FAK and these sites are required for PKL localization to focal adhesions and for paxillin binding. The absence of either FAK or Src-family kinases prevents PKL phosphorylation and suppresses localization of PKL but not GIT1 to focal adhesions after Rac activation. Expression of an activated FAK mutant in the absence of Src-family kinases partially restores PKL localization, suggesting that Src activation of FAK is required for PKL phosphorylation and localization. Overexpression of the nonphosphorylated GFP-PKL Triple YF mutant stimulates cell spreading and protrusiveness, similar to overexpression of a paxillin mutant that does not bind PKL, suggesting that failure to recruit PKL to focal adhesions interferes with normal cell spreading and motility.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCell Cycle ProteinsCell LineCell MovementFocal Adhesion Protein-Tyrosine KinasesFocal AdhesionsGenes, ReporterGTPase-Activating ProteinsIntercellular Signaling Peptides and ProteinsMiceOncogene ProteinsPaxillinPhosphoproteinsPhosphorylationProtein BindingAdaptor Proteins, Signal TransducingCell Cycle ProteinsFocal Adhesion Protein-Tyrosine KinasesGit2 protein, mouseGTPase-Activating ProteinsIntercellular Signaling Peptides and ProteinsNck proteinOncogene ProteinsPaxillinPhosphoproteinsPxn protein, mouseRecombinant Fusion Proteinssrc-Family KinasesTyrosine

Identifiers

PMID16000375
PMCPMC1196340
OpenAlexW2124169597

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.