SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins

TLDR

SH2 and SH3 domains are conserved noncatalytic modules in cytoplasmic signaling proteins that bind phosphotyrosine and mediate heteromeric complexes at the plasma membrane, thereby linking tyrosine kinases to downstream effectors and modulating interactions with the cytoskeleton and membrane. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.

Abstract

Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-γ, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.