Anticorpi Girdin

Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (PubMed:19211784, PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential for cell migration (PubMed:20462955, PubMed:16139227, PubMed:19211784, PubMed:21954290). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (PubMed:21954290). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (PubMed:27621449). Essential for the integrity of the actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382).

This gene encodes a member of the Girdin family of coiled-coil domain containing proteins. The encoded protein is an actin-binding protein that is activated by the serine/threonine kinase Akt and plays a role in cytoskeleton remodeling and cell migration. The encoded protein also enhances Akt signaling by mediating phosphoinositide 3-kinase (PI3K)-dependent activation of Akt by growth factor receptor tyrosine kinases and G protein-coupled receptors. Increased expression of this gene and phosphorylation of the encoded protein may play a role in cancer metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Expressed ubiquitously.

PEHO-like syndrome: An autosomal recessive syndrome characterized by microcephaly and moderately severe hypotonia manifesting at birth, seizures that progress into infantile spasms with hypsarrhythmia, brain atrophy with bilateral polymicrogyria and pachygyria, thin corpus callosum, and mild reduction in cerebellar vermis volume. Patients also display optic atrophy, severe cognitive delay, puffiness of the maxillary region of the face, and edema of the dorsum of the hands and feet.

Belongs to the CCDC88 family.

Phosphorylation is induced by epidermal growth factor (EGF) in a phosphoinositide 3-kinase (PI3K)-dependent manner (PubMed:16139227). Phosphorylation by AKT1/PKB is necessary for delocalization from the cell membrane and for cell migration (PubMed:16139227). Phosphorylated on tyrosine residues which promotes binding to phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a and enhances PI3K activity (PubMed:21954290). Tyrosine-phosphorylated by both receptor and non-receptor tyrosine kinases in vitro (PubMed:21954290). Tyrosine phosphorylation is required for AKT1-dependent phosphorylation of Ser-1417 (PubMed:21954290). Phosphorylation at Ser-1690 by PRKCQ disrupts interaction with GNAI3 and inhibits guanine nucleotide exchange factor activity (PubMed:23509302).

Cell membrane. Cytoplasm > Cytosol. Cytoplasmic vesicle. Cell projection > Lamellipodium. Cytoplasm > Cytoskeleton > Cilium basal body. Cytoplasm > Cytoskeleton > Microtubule organizing center > Centrosome > Centriole.

Localizes to the cytosol in unstimulated cells while EGF stimulation promotes membrane localization and guanine nucleotide exchange factor activity (PubMed:27864364). Localizes to the cell membrane through interaction with phosphoinositides (PubMed:16139227, PubMed:15882442).