Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
December 20, 1996Science

Association of Src Tyrosine Kinase with a Human Potassium Channel Mediated by SH3 Domain

View Full Paper
Ask AI
Bookmark
Share

Population

Cloned human Kv1.5 potassium channel (hKv1.5), native hKv1.5 in human myocardium, and cells coexpressing v-Src

Design

Preclinical

Authors

THTodd C. HolmesUniversity of California, IrvineDFDebra Ann FadoolFlorida State UniversityRRRuibao RenShanghai Jiao Tong University

Discussion

Loading...

Member takes

Implication

Src-hKv1.5 interaction may alter atrial repolarization; leaves open its role in human arrhythmias pending in vivo validation.

Key Points

  • To determine whether Src tyrosine kinase directly associates with and regulates the human Kv1.5 potassium channel through specific binding domains.
  • Assessed direct binding between Src tyrosine kinase and both cloned hKv1.5 and native hKv1.5 isolated from human myocardium.
  • Analyzed the structural interaction between the proline-rich motif of hKv1.5 and the SH3 domain of Src.
  • Measured hKv1.5 tyrosine phosphorylation levels and potassium channel currents in expression cells coexpressing v-Src.
  • Direct association occurred between Src tyrosine kinase and cloned as well as native myocardial hKv1.5, mediated by the channel's proline-rich motif and the kinase's SH3 domain.
  • Coexpression of v-Src induced tyrosine phosphorylation of hKv1.5 and suppressed potassium channel current.

Structured PICO

P
Population
Cloned human Kv1.5 potassium channel (hKv1.5), native hKv1.5 in human myocardium, and cells coexpressing v-Src
I
Intervention
Src tyrosine kinase (v-Src coexpression)
O
Outcome
Association of Src tyrosine kinase with hKv1.5, tyrosine phosphorylation, and channel current suppressionsurrogate

This study provides direct biochemical evidence for a signaling complex composed of a potassium channel (hKv1.5) and a protein tyrosine kinase (Src), which suppresses channel current.

Cite This Study

Holmes et al. (1996) studied this question.

synapsesocial.com/papers/6a704de9b27f158178274bbehttps://doi.org/10.1126/science.274.5295.2089
View Full Paper
Ask AI
Bookmark
Share

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Protein Kinase Activity Closely Associated with a Reconstituted Calcium-Activated Potassium Channel1991 · 177 citations
  2. 2Tyrosine phosphorylation of the Kv1.3 potassium channel1996 · 173 citations
  3. 3The voltage‐dependent K+ channel (Kv1.5) cloned from rabbit heart and facilitation of inactivation of the delayed rectifier current by the rat β subunit1995 · 22 citations
  4. 4Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated.1991 · 309 citations
  5. 5Identification of a Ten-Amino Acid Proline-Rich SH3 Binding Site1993 · 1,202 citations