Association of tyrosine phosphatase SHP-2 with F-actin at low cell densities

SHP-2 is an intracellular SH2 domain-containing protein-tyrosine phosphatas e with an essential role in cell signaling. Here we demonstrate that locali zation of SHP-2 is regulated by cell density in a cell adhesion-dependent m anner. When cells were plated at low densities, SHP-2 was distributed in Tr iton X-100-insoluble fractions, whereas it was totally soluble when cells w ere plated at high densities or when low density cells approached confluenc y. In all cases, the total protein level of SHP-2 was not changed. Fluoresc ent cell staining revealed that SHP-2 was co-localized with actin stress fi bers to the cell peripheral at low cell densities but was diffused in the e ntire cytoplasm at high cell densities. Transient transfection of cells wit h truncated forms of SHP-2 demonstrated that the catalytic domain of the en zyme was responsible for the density-regulated distribution of SHP-2, but t he catalytic activity was not required. An in vitro co-sedimentation study demonstrated direct binding of full-length and SH2 domain-truncated forms o f SHP-2 to F-actin. The data indicate that SHP-2 is regulated by cell densi ty and that it may have a role in assembling and disassembling of the actin network.