Evidence map›Paper›PMID 16227616›Full record

ArticleMolecular and cellular biology2005

Integrin alpha4beta1 promotes focal adhesion kinase-independent cell motility via alpha4 cytoplasmic domain-specific activation of c-Src.

Datsun A Hsia, Ssang-Taek Lim, Joie A Bernard-Trifilo, Satyajit K Mitra, Sakae Tanaka, Jeroen den Hertog, Daniel N Streblow, Dusko Ilic, Mark H Ginsberg, David D Schlaepfer

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

47 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Research Advances in the Role of the Tropomyosin Family in Cancer.International journal of molecular sciences · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. The Integrin Signaling Network Promotes Axon Regeneration via the Src-Ephexin-RhoA GTPase Signaling Axis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

10 authors at 6 institutions in 3 countries.

Datsun A HsiaThe Scripps Research Institute, Department of Immunology, IMM21, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Ssang-Taek Lim
Joie A Bernard-Trifilo
Satyajit K Mitra
Sakae Tanaka
Jeroen den Hertog
Daniel N Streblow
Dusko Ilic
Mark H Ginsberg
David D Schlaepfer
Scripps Research Institute · USHubrecht Institute for Developmental Biology and Stem Cell Research · NLOregon Health & Science University · USThe University of Tokyo · JPUniversity of California, San Diego · USUniversity of California, San Francisco · US

Funding

Role of Focal Adhesion Kinase In TumorigenesisR01CA102310 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHLAEPFER, DAVID D · 2003 to 2019
$5.0M
Regulation of Integrin Alpha4 BetalR01AR027214 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 1986 to 2010
$3.5M
Tyrosine Phosphorylation in Integrin SignalingR01CA075240 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHLAEPFER, DAVID D · 2003 to 2007
$1.9M
Role of FAK in Promoting Cell MotilityR01CA087038 · NCI · SCRIPPS RESEARCH INSTITUTE · PI SCHLAEPFER, DAVID D · 2001 to 2005
$1.7M
FN FAK SIGNALING AXIS AND TUMORIGENESISK01CA087652 · NCI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI ILIC, DUSKO · 2000 to 2004
$580k
PLATELETS IN RHEUMATIC DISEASER37AR027214 · NIAMS · SCRIPPS RESEARCH INSTITUTE · PI GINSBERG, MARK HOWARD · 1991 to 2000
$279k
TYROSINE PHOSPHORYLATION AND INTEGRIN SIGNALINGR29CA075240 · NCI · SCRIPPS RESEARCH INSTITUTE · PI SCHLAEPFER, DAVID D · 1997 to 2001
$259k
NCI NIH HHS CA 087652NCI NIH HHS CA 102310NCI NIH HHS CA 75240NCI NIH HHS CA 87038NCI NIH HHS K01 CA087652NCI NIH HHS R01 CA075240NCI NIH HHS R01 CA087038NCI NIH HHS R01 CA102310NCI NIH HHS R29 CA075240NIAMS NIH HHS AR 027214NIAMS NIH HHS R01 AR027214NIAMS NIH HHS R37 AR027214
6 · The paper itself

Abstract

The fibronectin binding integrins alpha5beta1 and alpha4beta1 generate signals pivotal for cell migration through distinct yet undefined mechanisms. For alpha5beta1, beta1-mediated activation of focal adhesion kinase (FAK) promotes c-Src recruitment to FAK and the formation of a FAK-Src signaling complex. Herein, we show that FAK expression is essential for alpha5beta1-stimulated cell motility and that exogenous expression of human alpha4 in FAK-null fibroblasts forms a functional alpha4beta1 receptor that promotes robust cell motility equal to the alpha5beta1 stimulation of wild-type and FAK-reconstituted fibroblasts. alpha4beta1-stimulated FAK-null cell spreading and motility were dependent on the integrity of the alpha4 cytoplasmic domain, independent of direct paxillin binding to alpha4, and were not affected by PRNK expression, a dominant-negative inhibitor of Pyk2. alpha4 cytoplasmic domain-initiated signaling led to a approximately 4-fold activation of c-Src which did not require paxillin binding to alpha4. Notably, alpha4-stimulated cell motility was inhibited by catalytically inactive receptor protein-tyrosine phosphatase alpha overexpression and blocked by the p50Csk phosphorylation of c-Src at Tyr-529. alpha4beta1-stimulated cell motility of triple-null Src(-/-), c-Yes(-/-), and Fyn(-/-) fibroblasts was dependent on c-Src reexpression that resulted in p130Cas tyrosine phosphorylation and Rac GTPase loading. As p130Cas phosphorylation and Rac activation are common downstream targets for alpha5beta1-stimulated FAK activation, our results support the existence of a novel alpha4 cytoplasmic domain connection leading to c-Src activation which functions as a FAK-independent linkage to a common motility-promoting signaling pathway.

Indexed as

Amino Acid SequenceAnimalsCell LineCell MovementCSK Tyrosine-Protein KinaseFibroblastsFocal Adhesion Protein-Tyrosine KinasesHumansIntegrin alpha4beta1Integrin alpha5beta1MiceMolecular Sequence DataPhosphorylationProtein-Tyrosine KinasesProto-Oncogene Proteins c-fynProto-Oncogene Proteins c-yesCSK protein, humanCSK Tyrosine-Protein KinaseFocal Adhesion Protein-Tyrosine KinasesIntegrin alpha4beta1Integrin alpha5beta1Protein-Tyrosine KinasesProto-Oncogene Proteins c-fynProto-Oncogene Proteins c-yessrc-Family Kinases

Identifiers

PMID16227616
PMCPMC1265817
OpenAlexW2133798544

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.