Fibroblast growth factor 9 secretion is mediated by a non-cleaved amino-terminal signal sequence

Fibroblast growth factors are a family of intercellular signaling molecules with multiple and varied roles in animal development. Most are exported fr om cells by means of a classical amino-terminal signal sequence that is cle aved from the mature protein during its passage through the secretory pathw ay. Fibroblast growth factor-9 (Fgf-g) does not contain a recognizable sign al sequence, although it is efficiently secreted. In this study, we show th at Fgf-g enters the endoplasmic reticulum and traverses the Golgi complex i n a similar manner to other constitutively secreted proteins.:Deletion and point mutation analysis has revealed an atypical non-cleaved signal sequenc e within the amino-terminal region of Fgf-9. Moreover, the first 28 amino a cids of Fgf-9 can function as an efficient non-cleaved signal peptide when appended to the amino terminus of green fluorescent protein.