Low M(r) phosphotyrosine protein phosphatase activity on fibroblast growth factor receptor is not associated with enzyme translocation

Fibroblast growth factor receptor (class IV) shares a certain degree of similarity with class III members like platelet- derived growth factor and macrophage-colony-stimulating factor receptors, which, once activated, are substrates of low Mr phosphotyrosine protein phosphatase. Up until now no phospho- tyrosine phosphatase has been shown to act on this receptor in vivo. Here we demonstrate that low Mr phosphotyrosine protein phosphatase is able to reduce receptor tyrosine phosphorylation and cell proliferation in response to basic fibroblast growth factor. Contrary to what was previously observed for platelet- derived growth factor, during cell stimulation with basic fibroblast growth factor, no enzyme redistribution among cellular compartments is observed. z 1999 Federation of European Biochemical Societies. growth factor receptor (EGFr) (class I receptor) has been previously evidenced in vitro (9), but we showed that this has no correspondence in vivo (10). We recently demonstrated that low Mr PTP undergoes a redistribution from the cytosol to the Triton X-100-insoluble fraction following cell stimulation with PDGF, and that in this fraction low Mr PTP exerts most of its activity on PDGFr (4). This phenomenon, in contrast, was not observed with EGF and, correspondingly, no eiect on EGFr activation was observed (10). These ¢ndings, taken together with the fact that EGFr is a substrate for this PTP in vitro, i.e. in a condition where the necessity of enzyme compartmentaliza- tion is overcome, seemed to stress the importance of intra- cellular localization of low Mr PTP in the de¢nition of en- zyme speci¢city in vivo. The high a⁄nity ¢broblast growth factor receptor (FGFr) family includes several members which bind more than one type of FGF. These receptors, though being allocated to a separate class (class IV), share several structure similarities with the members of class III, such that the ¢rst identi¢ed gene encoding FGFr was called £g, which stands for 'fms- like gene', where fms is the gene encoding M-CSFr. Here we demonstrate that these similarities extend also to the susceptibility of FGFr to low Mr PTP, as both receptor phosphorylation and mitogenic response elicited by the bind- ing of basic FGF (bFGF) were aiected by phosphatase over- expression. To our knowledge, this represents the ¢rst re- ported eiect of a tyrosine phosphatase on FGFr phosphorylation. When we veri¢ed the connection between the activity of low Mr PTP and its translocation in response to M-CSF or bFGF, no redistribution of the phosphatase was observed.