The ShcA phosphotyrosine docking protein uses distinct mechanisms to regulate myocyte and global heart function.

ABSTRACT:

Rationale

Although tyrosine kinases (TKs) are important for cardiac function, their relevant downstream targets in the adult heart are unknown. The ShcA docking protein binds specific phosphotyrosine (pTyr) sites on activated TKs through its N-terminal pTyr-binding (PTB) and C-terminal SH2 domains and stimulates downstream pathways through motifs such as pTyr sites in its central CH1 region. Therefore, ShcA could be a potential hub for downstream TK signaling in the myocardium.

Objective

To define the role of ShcA, a TK scaffold, in the adult heart using a myocardial-specific knockout of murine ShcA (ShcA CKO) and domain knock-in models.

Methods and results

ShcA CKO mice developed a dilated cardiomyopathy phenotype involving impaired systolic function with enhanced ca

SUBMITTER: Vanderlaan RD 

PROVIDER: S-EPMC3109628 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature