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]

The editors suggest the following Related Resources on Science sites:

VIRTUAL JOURNAL
The Association between Integrin-associated Protein and SHPS-1 Regulates Insulin-like Growth Factor-I Receptor Signaling in Vascular Smooth Muscle Cells

Laura A. Maile, Jane Badley-Clarke, and David R. Clemmons (1 September 2003)
Mol. Biol. Cell 14 (9), 3519. [DOI: 10.1091/mbc.E03-04-0239]
 |  Abstract »  |  Full Text »  |  PDF »