CFKBP SMAP - A NOVEL MOLECULE INVOLVED IN THE REGULATION OF SMOOTH-MUSCLE DIFFERENTIATION/

During embryogenesis, smooth muscle cells of the gut differentiate fro m mesenchymal cells derived from splanchnic mesoderm, We have isolated a gene involved in the differentiation of smooth muscle cells in the gut using differential display between the chicken proventriculus in w hich the smooth muscle layer develops poorly and the gizzard in which smooth muscles develop abundantly. The protein encoded by this gene sh owed highest similarity to mouse FK506 binding protein, FKBP65, and fr om the function of this protein it was designated chicken FKBP/smooth muscle activating protein (cFKBP/SMAP), cFKBP/SMAP was first expressed in smooth muscle precursor cells of the gut and, after smooth muscles differentiate, expression was restricted to smooth muscle cells. In o rgan culture of the gizzard, the differentiation of smooth muscle cell s was inhibited by the addition of FK506, the inhibitor of FKBPs. More over, overexpression of cFKBP/SMAP in lung and gizzard mesenchymal cel ls induced smooth muscle differentiation. In addition, cFKBP/SMAP-indu ced smooth muscle differentiation was inhibited by FK506, We postulate therefore that cFKBP/SMAP plays a crucial role in smooth muscle diffe rentiation in the gut and provides a powerful tool to study smooth mus cle differentiation mechanisms, which have been poorly analyzed so far .