Glial Growth Factor (GGF2) is also known as NRG1.
Structure
The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI.
Gene Ontology (GO) annotations related to this gene include signaling receptor binding and growth factor activity. An important paralog of this gene is NRG2.
Three dimensional structures for NRG1 Gene
Function
Diseases associated with NRG1 include Schizophrenia 6 and Lung Cancer. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and Signaling by ERBB2 KD Mutants.
NRG1 is the direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors and concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors.
The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development.
NRG1 binds to ERBB4 and also to ERBB3.
The gene acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4.
Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling.
It induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1.
Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons (By similarity).
Pathways
There are 58 pathways. Here are some of them.
14-3-3 Induced Intracellular Signaling
Actin-Based Motility by Rho Family GTPases
Activation of cAMP-Dependent PKA
Activation of PKA through GPCR
Activation of PKC through GPCR
Agrin Interactions at Neuromuscular Junction
Akt Signaling
Antioxidant Action of Vitamin-C
Apoptotic Pathways in Synovial Fibroblasts
Breast Cancer Regulation by Stathmin1
cAMP Pathway
Cellular Apoptosis Pathway
CREB Pathway
DHA Signaling
eIF2 Pathway
eNOS Signaling
Epithelial Adherens Junctions
ErbB Family Pathway
ErbB2-ErbB3 Heterodimers
ErbB4 Pathway
ERK Signaling
ERK5 Signaling
Estrogen Pathway
Glioma Invasiveness
GPCR Pathway
GSK3 Signaling
ILK Signaling
Intracellular Calcium Signaling
IP3 Pathway
JAK-STAT Pathway
JNK Pathway
MAPK Family Pathway
MAPK Signaling
Mitochondrial Apoptosis
Drugs
About NRG1, there are 35 pipelines under study, 21 of which have been approved.
Cisplatin is a platinum-based chemotherapy agent used to treat various sarcomas, carcinomas, lymphomas, and germ cell tumors.
Lapatinib is an antineoplastic agent and tyrosine kinase inhibitor used for the treatment of advanced or metastatic HER-positive breast cancer in patients who received prior chemotherapeutic treatments.
Paclitaxel is a taxoid chemotherapeutic agent used as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast and lung cancer.
Progesterone is a hormone used for a variety of functions, including contraception, control of abnormal uterine bleeding, maintenance of pregnancy, and prevention of endometrial hyperplasia.
Tamoxifen is a selective estrogen receptor modulator used to treat estrogen receptor positive breast cancer, reduce the risk of invasive breast cancer following surgery, or reduce the risk of breast cancer in high-risk women.
Pancrelipase is a purified form of porcine pancreatic lipase, amylase, and protease enzymes used to treat malabsorption associated with pancreatic insufficiency resulting from cystic fibrosis and pancreatitis.
Afatinib is an antineoplastic agent used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with non-resistant EGFR mutations or resistance to platinum-based chemotherapy.
Alteplase is a recombinant form of human tissue plasminogen activator used in the emergency treatment of myocardial infarction, ischemic stroke, and pulmonary emboli.
Bupivacaine is a local anesthetic used in a wide variety of superficial and invasive procedures.
Carboplatin is a alkylating agent used to treat advanced ovarian cancer.
Colchicine is an alkaloid used in the symptomatic relief of pain in attacks of gout and to treat the inflammatory symptoms of Familial Mediterranean Fever (FMF).
