Tyrosine phosphatase SHP-2 dephosphorylates the platelet-derived growth factor receptor but enhances its downstream signalling

SHP-2 is a widely distributed Src homology 2 (SH2) domain-containing tyrosi ne phosphatase that is recruited to growth factor receptors on stimulation. We have transiently co-expressed several catalytically active and inactive forms of the enzyme with the platelet-derived growth. factor (PDGF) recept or in human embryonic kidney 293 cells. The catalytically active forms of S HP-2 decreased the tyrosine phosphorylation of the receptor, whereas the ca talytically inactive forms increased the phosphorylation. However, PDGF-ind uced activation of the mitogen-activated protein (MAP) kinase pathway was e nhanced by the active forms of SHP-2 but decreased by the inactive forms. T he results suggest that the PDGF receptor is a physiological substrate of S HP-2 and that SHP-2 has a positive role in the PDGF-stimulated activation o f MAP kinase. The dissociation of the receptor phosphorylation from the act ivation of MAP kinase suggests that signalling through growth factor recept ors does not depend merely on their tyrosine phosphorylation.