Domain

PLC-gamma, N-terminal SH2 domain (IPR035024)

Short name: PLC-gamma_N-SH2

Overlapping homologous superfamilies

Domain relationships

  • SH2 domain (IPR000980)
    • PLC-gamma, N-terminal SH2 domain (IPR035024)

Description

This entry represents the N-terminal SH2 domain of phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma (PLC-gamma).

PLC-gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLC-gamma is composed of a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases [PMID: 19665973].

SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLC-gamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium [PMID: 19665973]. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated site [PMID: 19926274].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
CDD
  • cd10341 (SH2_N-SH2_PLC_gamma_like)