GAB2 - Function

Function

GAB2 mediates the interactions between receptor tyrosine kinases (RTK) or non-RTK receptors, such as G protein coupled receptors, cytokine receptors, multichain immune recognition receptors and integrins, and the molecules of the intracellular signaling pathways. By providing a platform to host a wide array of interactions from extracellular inputs to intracellular pathways, GAB proteins can act as a gatekeeper to the cell, modulating and integrating signals as they pass them along, to control the functional state within the cell.

Mutagenesis and Binding assays have helped to identify which molecules and what pathways are downstream of GAB2. The two main pathways of GAB proteins are SHP2 and PI3K. GAB protein binding to SHP2 molecules acts as an activator whose main effect is the activation of the ERK/MAPK pathway. There are also, however other pathways that are activated by this interaction such as the pathways c-Kit-induced Rac activation and β1-integrin. PI3K activation by GAB2 promotes cell growth. The effects of all the pathways activated by GAB proteins are not known, but it is easy to see that amplification of signal can progress quickly and these proteins can have large effects on the state of the cell. While not lethal, GAB2 deficient knockout mice do exhibit phenotypic side-effects. These include weak allergic reactions, reduced mast cell growth in bone marrow and osteopetrosis. Knockout mice have also been used to show the importance of GAB2 in maintenance of cardiac function. A paracrine factor, NRG1 β, utilizes GAB2 to activate the ERK and AKT pathways in the heart to produce angiopoietin 1.