TGF alpha

Transforming growth factor, alpha
250px PDB rendering based on 1mox.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1GK5, 1MOX, 1YUF, 1YUG, 2TGF, 3E50, 3TGF, 4TGF
Identifiers
Symbols	TGFA ; TFGA
External IDs	OMIM: 190170 MGI: 98724 HomoloGene: 2431 GeneCards: TGFA Gene
Gene ontology Molecular function • glycoprotein binding • epidermal growth factor receptor binding • protein binding • growth factor activity Cellular component • extracellular space • nucleus • plasma membrane • integral component of plasma membrane • cell surface • basolateral plasma membrane • cytoplasmic vesicle • perinuclear region of cytoplasm Biological process • activation of MAPK activity • angiogenesis • epidermal growth factor receptor signaling pathway • cell proliferation • wound healing • response to drug • negative regulation of apoptotic process • positive regulation of epidermal growth factor-activated receptor activity • positive regulation of mitotic nuclear division • positive regulation of epithelial cell proliferation • mammary gland alveolus development • hepatocyte proliferation Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE TGFA 205016 at tn.png
File:PBB GE TGFA 205015 s at tn.png
File:PBB GE TGFA 211258 s at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7039	21802
Ensembl	ENSG00000163235	ENSMUSG00000029999
UniProt	P01135	P48030
RefSeq (mRNA)	NM_001099691	NM_031199
RefSeq (protein)	NP_001093161	NP_112476
Location (UCSC)	Chr 2: 70.45 – 70.55 Mb	Chr 6: 86.2 – 86.28 Mb
PubMed search	[1]	[2]

Transforming growth factor alpha (TGF-α) is a protein that in humans is encoded by the TGFA gene. As a member of the epidermal growth factor (EGF) family, TGF-α is a mitogenic polypeptide. The protein becomes activated when binding to receptors capable of protein kinase activity for cellular signaling.

TGF-α is a transforming growth factor that is a ligand for the epidermal growth factor receptor, which activates a signaling pathway for cell proliferation, differentiation and development. This protein may act as either a transmembrane-bound ligand or a soluble ligand. This gene has been associated with many types of cancers, and it may also be involved in some cases of cleft lip/palate.

Synthesis

TGF-α is synthesized internally as part of a 160 (human) or 159 (rat) amino acid transmembrane precursor. The precursor is composed of an extracellular domain containing a hydrophobic transmembrane domain, 50 amino acids of TGF-α, and a 35-residue-long cytoplasmic domain. In its smallest form TGF-α has six cysteines linked together via three disulfide bridges. Collectively all members of the EGF/TGF-α family share this structure. The protein, however, is not directly related to TGF-β. In the stomach, TGF-α is manufactured within the normal gastric mucosa. TGF-α has been shown to inhibit gastric acid secretion.

Limited success has resulted from attempts to synthesize of a reductant molecule to TGF-α that displays a similar biological profile.

Synthesis in the stomach

In the stomach, TGF-α is manufactured within the normal gastric mucosa. TGF-α has been shown to inhibit gastric acid secretion.

Function

TGF-α can be produced in macrophages, brain cells, and keratinocytes. TGF-α induces epithelial development. Considering that TGF-α is a member of the EGF family, the biological actions of TGF-α and EGF are similar. For instance, TGF-α and EGF bind to the same receptor. When TGF-α binds to EGFR it can initiate multiple cell proliferation events. Cell proliferation events that involve TGF-α bound to EGFR include wound healing and embryogenesis. TGF-α is also involved in tumerogenesis and believed to promote angiogenesis.

TGFα has also been shown to stimulate neural cell proliferation in the adult injured brain.

TGF-α receptor

A 170-kDa glycosylated protein known as the EGF receptor binds to TGF-α allowing the polypeptide to function in various signaling pathways. The EGF receptor is characterized by having an extracellular domain that has numerous amino acid motifs. EGFR is essential for a single transmembrane domain, an intracellular domain (containing tyrosine kinase activity), and ligand recognition. As a membrane anchored-growth factor, TGF-α can be cleaved from an integral membrane glycoprotein via a protease. Soluble forms of TGF-α resulting from the cleavage have the capacity to activate EGFR. EGFR can be activated from a membrane-anchored growth factor as well.

When TGF-α binds to EGFR it dimerizes triggering phosphorylation of a protein-tyrosine kinase. The activity of protein-tyrosine kinase causes an autophosphorylation to occur among several tyrosine residues within EGFR, influencing activation and signaling of other proteins that interact in many signal transduction pathways.

File:EGFR signaling pathway.png

Epidermal growth factor receptor (EGFR) signaling pathway upon binding to TGF-α.

Animal studies

In an animal model of Parkinson's disease where dopaminergic neurons have been damaged by 6-hydroxydopamine, infusion of TGF-α into the brain caused an increase in the number of neuronal precursor cells. However TGF-α treatment did not result in neurogenesis dopaminergic neurons.

Human studies

TGF-α and the neuroendocrine system

The EGF/TGF-α family has been shown to regulate luteinizing hormone-releasing hormone (LHRH) through a glial-neuronal interactive process. Produced in hypothalamic astrocytes, TGF-α indirectly stimulates LHRH release through various intermediates. As a result, TGF-α is a physiological component essential to the initiation process of female puberty.

TGF-α and the suprachiasmatic nucleus

TGF-α has also been observed to be highly expressed in the suprachiasmatic nucleus (SCN) (5). This finding suggests a role for EGFR signaling in the regulation of CLOCK and circadian rhythms within the SCN. Similar studies have shown that when injected into the third ventricle TGF-α can suppress circadian locomotor behavior along with drinking or eating activities.

TGF-α and tumors

Its potential use as a prognostic biomarker in various tumors, like gastric carcinoma . or melanoma has been suggested.

Interactions

TGF alpha has been shown to interact with GORASP1 and GORASP2.

See also

• Transforming growth factor

External links

• Transforming Growth Factor alpha at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.