Modulation of intracellular transport of acidic fibroblast growth factor by mutations in the cytoplasmic receptor domain

Endocytic uptake and intracellular transport of acidic fibroblast growth fa ctor (aFGF) was studied :in cells transfected with FGF receptor 4 with muta tions in the cytoplasmic part. Endocytic uptake in HeLa cells was reduced b ut not abolished when the tyrosine kinase of the receptor was inactivated b y mutations or deletions. The tyrosine kinase-dependent endocytosis of aFGF was prevented by the expression of a dominant negative dynamin mutant that blocks endocytosis from coated pits and caveolae, However, more than half of the total endocytic uptake of aFGF was not affected under these conditio ns, indicating an endocytic uptake mechanism not involving coated pits or c aveolae, Mutation or deletion of a putative caveolin-binding sequence did n ot prevent the localization of part of the receptors to a low density, cave olin-containing subcellular fraction. Whereas wild-type receptor transfers the growth factor from early endosomes to the recycling compartment, kinase negative, full length receptors were inefficient in this respect and the g rowth factor instead accumulated in lysosomes, By contrast, when most of th e intracellular part of the receptor, including the kinase domain, was remo ved, aFGF was transported to the recycling compartment, as in cells that ex press wild-type receptors, suggesting the presence of a kinase-regulated ta rgeting signal in the cytoplasmic tail.