Cyr61, product of a growth factor-inducible immediate early gene, is associated with the extracellular matrix and the cell surface.

cyr61 is a specific target for activation by platelet-derived growth factor and fibroblast growth factor and is inducible by the oncogene v-src. It is a member of the class of immediate early genes that includes those encoding protooncogene products, transcription factors, and cytokines. We have previously characterized the synthesis and degradation of the cyr61-encoded mRNA and protein. Although the deduced Cyr61 protein sequence contains an NH2-terminal secretory signal, it is not detectable in the conditioned medium of serum-stimulated cells. We show here that in rapidly growing cell cultures, newly synthesized Cyr61 is secreted and is associated with both the extracellular matrix and the cell surface. In contrast, Cyr61 secreted in serum-stimulated quiescent cells is directed to the cell surface and is hot incorporated into the extracellular matrix. Once associated with the extracellular matrix, Cyr61 has a half-life of greater than 24 h, whereas intracellular and cell surface-associated Cyr61 has an apparent half-life of approximately 30 min. Furthermore, Cyr61 appears to bind heparin with high affinity. These observations suggest similarities among Cyr61, the fibroblast growth factors (heparin-binding growth factors), and the protooncogene product Int-1 and are consistent with the hypothesis that Cyr61 plays a role in cell-cell communication involving the interaction of neighboring cells.