Sci. STKE, 23 September 2003
PHOSPHATASES Signal Duration
In the many signaling cascades that involve phosphorylation, there are phosphatases to counter the kinases. However, phosphatases may not simply be required to terminate a signal, but may actually contribute to setting the cellular response. Maile et al. show that the recruitment of the phosphatase SHP-2 to the insulin-like growth factor receptor (IGF-1R) is essential for smooth muscle cell (SMC) responses to the IGF-1. The recruitment of SHP-2 was indirect, requiring interaction between the transmembrane proteins IAP (integrin-associated protein) and SHPS-1 (Src homology domain containing protein tyrosine phosphatase substrate-1). Disruption of the IAP and SHPS-1 interaction by application of antibodies or overexpression of IAP mutants resulted in decreased SHPS-1 phosphorylation and SHP-2 recruitment to SHPS-1. These treatments also increased the duration of IGF-1R phosphorylation. Blocking the recruitment of SHP-2 by interfering with the IAP-SHPS-1 interaction inhibited mitogen-activated protein kinase phosphorylation, cell proliferation, and cell migration in response to IGF-1. SMC responses to platelet-derived growth factor were unaffected by disruption of IAP and SHPS-1 interaction. Thus, not only do phosphatases play an important role in terminating kinase cascades, but they also contribute to the cellular response to growth factors.
L. A. Maile, J. Badley-Clarke, D. R. Clemmons, The association between integrin-associated protein and SHPS-1 regulates insulin-like growth factor-I receptor signaling in vascular smooth muscle cells. Mol. Biol. Cell 14, 3519-3528 (2003). [Abstract] [Full Text]
Citation: Signal Duration. Sci. STKE 2003, tw367 (2003).
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