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Grb2-associated binding proteins (Gab) are a new family of proteins involved in
signaling events triggered by numerous stimuli, including growth factors, cytokines, T cell and B
cell antigens (Yan liu and Larry, 2002). The mammalian Gab protein (Human isoforms:
Gab1, Gab2, Gab3), along with their homolog DOS
(Drosophila) and Soc 1 (Caenorhabditis
elegans), belongs to a family of scaffolding proteins closely related to IRS, FRS2, LAT
and Dok (White, 1998; Huyer and Alexander, 1999; Hibi and Horano, 2000; and Zhang
and samelson, 2000). They have multifunctional docking sites for other signaling proteins
that transmit signals to downstream effector molecules that ultimately regulate cell growth
and differentiation. Gab knockout mice reveal distinct functions for individual Gab proteins.
For instance, Gab1, which is expressed ubiquitously, appears to be indispensable
for embryonic development, such that Gab1_/_ mice die at an early phase of development
with multiple defects in heart, placenta, liver, spleen and muscle development, probably due
to the combined effect of defective EGF, Platelet Derived Growth Factor (PDGF), HGF
and gp130 signaling (Itoh et al., 2000; and Sachs et al., 2000). In contrast,
Gab2_/_ and Gab3_/_ mice are viable and have a normal life span.
Hematopoiesis is largely normal in both mice, but
Gab2_/_ mice have a defect in mast cell signaling, while the loss of Gab3 does not result in detectable defects in
development or immune system function. This shows that different members of this scaffolding
proteins exert different physiological responses by tethering pathway components together and
relay signals that are cell-specific. In this review, we focus briefly on their structure and
role in physiological responses.
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