Background: The mammalian Grb2 adaptor protein binds pTyr-X-Asn motifs through its SH2 domain, and engages downstream targets such as Sos1 and Gab1 through its SH3 domains.
The ability of these GTPases to signal requires that the GTP-bound form engage downstream effectors, interactions that occur only on the cytosolic surface of cellular membranes.
Visuomotor circuits filter visual information and determine whether or not to engage downstream motor modules to produce behavioral outputs.
POMC and NPY/Agrp neurons engage downstream targets, such as in the paraventricular hypothalamic nucleus, that possess the melanocortin receptor (MC4R).
Class IA PI3Ks catalyze the synthesis of the lipid second messenger phosphatidylinositol (3,4,5 -triphosphate (PIP3,4,5 -triphosphateownstream effectors such as the PIP3ein kinase B (PKB) pathwhichShengageset al., 1998; Vanhaesebroeck et al., 2005).
CLEC12A is a C-type lectin receptor (CLR) belonging to a family of transmembrane proteins that recognize pathogen-associated molecular patterns and engage downstream immune signal transduction pathways (Dambuza and Brown, 2015; Osorio and Reis e Sousa, 2011).
On the other hand, phase-advanced photoentrainment in Six3-Cre Lhx1lox/lox mice, with an activity onset before dark, suggests that the Lhx1-deficient SCN does engage downstream oscillators when driven by light.
Four adaptor proteins (myeloid differentiation factor (MyD 88, MyD88-adaptor-like/TIR domain-containing adaptor protein (MAL/TIRAP) [ 7], TIR domain-containing adaptor inducing interferon-β (TRIF) and TRIF-related adaptor molecule (TRAM) [ 8, 9]) transduce signals from all of the TIR domains and engage downstream signaling proteins.
Our investigations suggest that GRASP65 cleavage contributes to apoptotic signalling via release of membrane distal caspase cleavage fragments that translocate to the mitochondria and engage downstream execution phase processes, and we identify Bcl-XL as a candidate apoptotic GRASP65 binding partner.
Furthermore, it is now acknowledged that Shc, by interacting with proteins other than Grb2 such as IQGAP1, Crk and Sgk269, can promote Grb2-independent pathways and functions [ 13, 17- 19], underscoring the complexity of the cellular networks that these adaptor proteins can engage downstream of RTKs.
