tailieunhanh - Fibroblast growth factor phosphorylation and receptors in rod outer segments

In addition specific binding sites for exogenous FGFs have been identified on ROS and disc membranes. A single high affinity site with a Kd of 40 pM was present in intact ROS while an additional low affinity site with a Kd of 300-600 pM was present in leaky ROS or in disc membranes. | The EMBO Journal - 2273, 1989 Fibroblast growth factor phosphorylation and in rod outer segments , and Unite de Recherches Gerontologiques, INSERM U. 118, Centre de Gerontologie Claude-Bernard, 29, rue Wilhem, 75016 Paris, France Communicated by Acidic and basic fibroblast growth factors (aFGF and bFGF) have been isolated and purified from rod outer segments (ROS). aFGF is tightly bound to ROS membranes and can be specifically released by ATP. We show that this mechanism is dependent on the phosphorylation of aFGF itself. Phorbol 12-myristate 13-acetate (PMA) enhances this phenomenon independently of rhodopsin phosphorylation. This demonstrates that aFGF release from ROS membranes is dependent on its phosphorylation by endogenous kinase C. In addition specific binding sites for exogenous FGFs have been identified on ROS and disc membranes. A single high affinity site with a Kd of 40 pM was present in intact ROS while an additional low affinity site with a Kd of 300-600 pM was present in leaky ROS or in disc membranes. Light or ATP modified neither these Kd nor the apparent number of sites. The presence of specific receptors for FGFs and the kinase C dependent release of endogenous membrane bound aFGF suggest an autocrine mechanism which may be involved in photoreceptor cell biology. Key words: fibroblast growth factor/phosphorylation/kinase C/photoreceptor/receptor Introduction Fibroblast growth factors (FGFs) have been implicated in neuronal development and survival after their identification as potent mitogens for many mesenchymal or ectodermal cells. They are thus multifunctional (reviews in Gospodarowicz and Schweigerer, 1986; Spom and Roberts, 1988). FGF receptors have been localized on various cell types which are stimulated to divide by these growth factors. A plasma membrane associated receptor with a molecular weight of 125-145 kd (Neufeld and Gospodarowicz, 1985; Moscatelli, 1986; Moenner