Interest in the diverse biology of protein
tyrosine phosphatases that are encoded by more than 100
genes in the human genome continues to grow at an
accelerated pace. In particular, two cytoplasmic protein
tyrosine phosphatases composed of two Src homology 2
(SH2) NH2-terminal domains and a C-terminal proteintyrosine
phosphatase domain referred to as SHP-1 and
SHP-2 are known to govern a host of cellular functions.
SHP-1 and SHP-2 modulate progenitor cell
development, cellular growth, tissue inflammation, and
cellular chemotaxis, but more recently the role of SHP-1
and SHP-2 to directly control cell survival involving
oxidative stress pathways has come to light. SHP-1 and
SHP-2 are fundamental for the function of several
growth factor and metabolic pathways yielding far
reaching implications for disease pathways and disorders
such as diabetes, neurodegeneration, and cancer.
Although SHP-1 and SHP-2 can employ similar or
parallel cellular pathways, these proteins also clearly
exert opposing effects upon downstream cellular
cascades that affect early and late apoptotic programs.
SHP-1 and SHP-2 modulate cellular signals that involve
phosphatidylinositol 3-kinase, Akt, Janus kinase 2,
signal transducer and activator of transcription proteins,
mitogen-activating protein kinases, extracellular signalrelated
kinases, c-Jun-amino terminal kinases, and nuclear factor-kB. Our progressive understanding of the
impact of SHP-1 and SHP-2 upon multiple cellular
environments and organ systems should continue to
facilitate the targeted development of treatments for a
variety of disease entities