FHL2

Sphingosine kinase-1 (SK1) is a key enzyme that catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). SK1, and its product S1P, regulate numerous and diverse biological functions, including cell growth, differentiation, proliferation, and apoptosis. S1P also plays a central role in cardiac development and ischemic preconditioning. FHL2 (SLIM3) has been identified as a SK1-interacting protein in mammalian cardiomyocytes. FHL2, but not FHL1 or FHL3, interacts with SK1, and FHL2 colocalizes with SK1 in the cytoplasm of these cells. The interaction of FHL2 with SK-1 involves the C-terminal portion of SK1. Overexpression of FHL2 has been found to attneuate the activity and antiapoptotic effects of SK1. Endothelin-1, a potent survival factor in cardiomyocytes, inhibits FHL2-SK1 association and increases SK1 activity. FHL2 is therefore a novel inhibitor of SK1 activity in cardiomyocytes and targeting FHL2 may prevent myocardial apoptosis through activation of SK1.A transcriptional coactivator, FHL2 is also known to form complexes consisting of Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1), FHL2, and androgen receptors (AR) in prostate cancer cells, perhaps functioning as a molecular adaptor with PELP1 in the progression of prostate cancer.