Evidence map›Paper›PMID 19887442›Full record

ArticleThe Journal of biological chemistry2010

Alpha5beta1 integrin engagement increases large conductance, Ca2+-activated K+ channel current and Ca2+ sensitivity through c-src-mediated channel phosphorylation.

Yan Yang, Xin Wu, Peichun Gui, Jianbo Wu, Jian-Zhong Sheng, Shizhang Ling, Andrew P Braun, George E Davis, Michael J Davis

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

27 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Vascular mechanotransduction.Physiological reviews · 2023
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Calcium- and voltage-gated BK channels in vascular smooth muscle.Pflugers Archiv : European journal of physiology · 2018
    Review
  11. Tyrphostin AG556 increases the activity of large conductance CaJournal of cellular and molecular medicine · 2017
    Article
  12. KCa1.1 channels regulate βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2013
    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

9 authors at 3 institutions in 2 countries.

Yan YangDepartment of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri 65212, USA.
Xin Wu
Peichun Gui
Jianbo Wu
Jian-Zhong Sheng
Shizhang Ling
Andrew P Braun
George E Davis
Michael J Davis
University of Missouri · USUniversity of Calgary · CATexas A&M Health Science Center · US

Funding

Regulation of Vascular Tone and Ca Channels by IntegrinsR01HL072989 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI DAVIS, MICHAEL JOHN · 2003 to 2009
$1.8M
IMPROV OF RES FACIL: STEM CELLC06RR017353 · NCRR · UNIVERSITY OF MISSOURI-COLUMBIA · PI CRIST, WILLIAM M · 2002 to 2002
$1.7M
Regulation of Arteriolar Tone &K Channels by IntegrinsR01HL071796 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI DAVIS, MICHAEL JOHN · 2003 to 2006
$1.2M
CIHRNCRR NIH HHS C06 RR017353NCRR NIH HHS RR-017353NHLBI NIH HHS HL-71796NHLBI NIH HHS HL-72989NHLBI NIH HHS R01 HL071796NHLBI NIH HHS R01 HL072989
6 · The paper itself

Abstract

Large conductance, calcium-activated K(+) (BK) channels are important regulators of cell excitability and recognized targets of intracellular kinases. BK channel modulation by tyrosine kinases, including focal adhesion kinase and c-src, suggests their potential involvement in integrin signaling. Recently, we found that fibronectin, an endogenous alpha5beta1 integrin ligand, enhances BK channel current through both Ca(2+)- and phosphorylation-dependent mechanisms in vascular smooth muscle. Here, we show that macroscopic currents from HEK 293 cells expressing murine BK channel alpha-subunits (mSlo) are acutely potentiated following alpha5beta1 integrin activation. The effect occurs in a Ca(2+)-dependent manner, 1-3 min after integrin engagement. After integrin activation, normalized conductance-voltage relations for mSlo are left-shifted at free Ca(2+) concentrations >or=1 microm. Overexpression of human c-src with mSlo, in the absence of integrin activation, leads to similar shifts in mSlo Ca(2+) sensitivity, whereas overexpression of catalytically inactive c-src blocks integrin-induced potentiation. However, neither integrin activation nor c-src overexpression potentiates current in BK channels containing a point mutation at Tyr-766. Biochemical tests confirmed the critical importance of residue Tyr-766 in integrin-induced channel phosphorylation. Thus, BK channel activity is enhanced by alpha5beta1 integrin activation, likely through an intracellular signaling pathway involving c-src phosphorylation of the channel alpha-subunit at Tyr-766. The net result is increased current amplitude, enhanced Ca(2+) sensitivity, and rate of activation of the BK channel, which would collectively promote smooth muscle hyperpolarization in response to integrin-extracellular matrix interactions.

Indexed as

Amino Acid SubstitutionAnimalsCalciumCell LineEnzyme ActivationFibronectinsHumansIntegrin alpha5beta1Ion Channel GatingLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsMiceMolecular Sequence DataMutationPhosphorylationPhosphotyrosineProto-Oncogene Proteins pp60(c-src)AG 1879CalciumFibronectinsIntegrin alpha5beta1Kcnma1 protein, mouseLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsPhosphotyrosineProto-Oncogene Proteins pp60(c-src)Pyrimidines

Identifiers

PMID19887442
PMCPMC2804158
OpenAlexW1992550839

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.