Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell.

摘要: Follistatin (FS), an activin-binding protein, is a monomer derived from two polypeptide core sequences of 315 (FS-315) and 288 (FS-288) amino acids originated alternatively spliced mRNA. To define the structural heterogeneity native FS, we purified six molecular forms FS porcine ovaries. Protein chemical analysis revealed that differences among isoforms were caused by truncation carboxyl-terminal region and/or presence carbohydrate chains, resulting in formation FS-315, FS-288, composed 303 (FS-303) various glycosylation on potential Asn-linked sites. The majority isolated ovaries was FS-303, which may have been FS-315 proteolytic cleavage 12 COOH-terminal acids. All species almost same activin binding activity (Kd = 540-680 pM). By contrast, truncated form, showed much higher affinity for rat granulosa cell surface than whereas had no affinity. FS-288 bound to heparan sulfate-Sepharose CL-4B, but did not, suggesting bind sulfate proteoglycans cell. COS cells transfected with DNA expressed adhered surface, secreted protein into medium, not surface. In anterior pituitary culture, (ED50 2 ng/ml) more potent suppressing follicle-stimulating hormone release FS-303 10 20 ng/ml). These results suggest cell-associated traps tightly matrix, thereby effectively blocking plays important role controlling actions paracrine or autocrine manner.