Role of SHP1 as a Tumor Suppressor in Human Mammary Tumorigenesis.

摘要

SHP-1, the Src homology 2-containing protein tyrosine phosphotase 1, involves in the dephosphorylation of growth factor-receptors or non-receptor protein tyrosine kinases and serves as a negative regulator of proliferative signaling in cells. In addition, PI3K signaling pathway plays an important role in growth factor-mediated cell survival and proliferation. To investigate the regulation of PI3K signaling in malignant epithelial cells, we studied the interaction of SHP-1 with multiple mediators in the cascade, including PI3K, PTEN and AKT. In SKBr3 cells, we observed a growth factor-stimulation induced association of SHP-1 with PTEN. Further study revealed that binding of SHP-1 to PTEN was enhanced by LCK, a Src family tyrosine kinase, suggesting a tyrosine phosphorylation-mediated interaction between the two proteins. In order to investigate the regulation of SHP-1 on PTEN, we coexpressed wild type SHP-1 or inactive mutant SHP-1 with PTEN in cells.