Disease relevance of Ppp3r1

• MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction [1].

High impact information on Ppp3r1

• In these mice, calcineurin function is removed by the selective deletion of Cnb1 in the mesenchyme of the developing urinary tract using the Cre/lox system [2].
• However, the protein kinases that function downstream of MEKK3 to mediate MCIP1 phosphorylation and the mechanism of MCIP1-mediated calcineurin regulation have not been defined [3].
• In neonatal cultured cardiac myocytes, inhibition of GCA by HS142-1 (100 microg/mL) increased basal and phenylephrine (10(-6) mol/L)-stimulated calcineurin activity, nuclear translocation of NFATc3, and MCIP1 mRNA expression [4].
• METHODS AND RESULTS: At 14 weeks of age, calcineurin activity, nuclear translocation of nuclear factor of activated T cells c3 (NFATc3), and modulatory calcineurin-interacting protein 1 (MCIP1) gene expressions were increased in the hearts of GCA-KO mice compared with wild-type (WT) mice [4].
• To address these questions, transgenic (TG) mice engineered to overexpress modulatory calcineurin-interacting protein-1 (MCIP1) in the myocardium were used to achieve cardiac-specific inhibition of calcineurin activation [1].

Biological context of Ppp3r1

• In summary, our findings reveal a previously unrecognized essential regulatory role of mitogen-activated protein kinase signaling in calcineurin activation through the reversible phosphorylation of a calcineurin-interacting protein, MCIP1 [3].

References