TGF alpha

TGFA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GK5, 1MOX, 1YUF, 1YUG, 2TGF, 3E50, 3TGF, 4TGF
Identifiers
Aliases	TGFA, TFGA, transforming growth factor alpha, Transforming growth factor - α
External IDs	OMIM: 190170 MGI: 98724 HomoloGene: 2431 GeneCards: TGFA
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p13.3 Start 70,447,284 bp[1] End 70,554,193 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 D1|6 37.62 cM Start 86,172,205 bp[2] End 86,252,701 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pancreatic ductal cell islet of Langerhans amniotic fluid corpus callosum periodontal fiber gallbladder gums oral cavity inferior olivary nucleus secondary oocyte Top expressed in olfactory tubercle lip nucleus accumbens belly cord globus pallidus suprachiasmatic nucleus pyloric antrum epithelium of stomach Jacobson's organ esophagus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function epidermal growth factor receptor binding protein binding growth factor activity Cellular component integral component of membrane endoplasmic reticulum membrane membrane plasma membrane integral component of plasma membrane extracellular region cell surface basolateral plasma membrane perinuclear region of cytoplasm ER to Golgi transport vesicle membrane endoplasmic reticulum-Golgi intermediate compartment membrane cytoplasmic vesicle Golgi membrane extracellular space clathrin-coated vesicle membrane Biological process positive regulation of epidermal growth factor-activated receptor activity positive regulation of epithelial cell proliferation endoplasmic reticulum to Golgi vesicle-mediated transport COPII vesicle coating cell population proliferation positive regulation of mitotic nuclear division positive regulation of cell division regulation of transcription by RNA polymerase II epidermal growth factor receptor signaling pathway positive regulation of cell population proliferation MAPK cascade signal transduction negative regulation of epidermal growth factor receptor signaling pathway positive regulation of protein kinase B signaling membrane organization intracellular signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7039 21802 Ensembl ENSG00000163235 ENSMUSG00000029999 UniProt P01135 P48030 RefSeq (mRNA) NM_001099691 NM_001308158 NM_001308159 NM_003236 NM_031199 RefSeq (protein) NP_001093161 NP_001295087 NP_001295088 NP_003227 NP_112476 NP_001390047 Location (UCSC) Chr 2: 70.45 – 70.55 Mb Chr 6: 86.17 – 86.25 Mb PubMed search [3] [4]
Wikidata
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Transforming growth factor alpha (TGF-α) is a protein that in humans is encoded by the TGFA gene.^[5] As a member of the epidermal growth factor (EGF) family, TGF-α is a mitogenic polypeptide.^[6] 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.^[5]

Synthesis

TGF-α is synthesized internally as part of a 160 (human) or 159 (rat) amino acid transmembrane precursor.^[7] 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.^[7] 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.

Limited success has resulted from attempts to synthesize of a reductant molecule to TGF-α that displays a similar biological profile.^[8]

Synthesis in the stomach

In the stomach, TGF-α is manufactured within the normal gastric mucosa.^[9] 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.^[8] 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.^[7]

TGF-α has also been shown to stimulate neural cell proliferation in the adult injured brain.^[10]

Receptor

A 170-kDa glycosylated protein known as the EGF receptor binds to TGF-α allowing the polypeptide to function in various signaling pathways.^[6] 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.^[6] As a membrane anchored-growth factor, TGF-α can be cleaved from an integral membrane glycoprotein via a protease.^[7] 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.

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.^[10] However TGF-α treatment did not result in neurogenesis of dopaminergic neurons.^[11]

Human studies

Neuroendocrine system

The EGF/TGF-α family has been shown to regulate luteinizing hormone-releasing hormone (LHRH) through a glial-neuronal interactive process.^[6] 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.^[6]

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.^[12] Similar studies have shown that when injected into the third ventricle TGF-α can suppress circadian locomotor behavior along with drinking or eating activities.^[12]

Tumors

This protein shows potential use as a prognostic biomarker in various tumors, like gastric carcinoma.^[13] or melanoma has been suggested.^[14] Elevated TGF-α is associated with Menetrier's disease, a precancerous condition of the stomach.^[15]

Interactions

TGF alpha has been shown to interact with GORASP1^[16] and GORASP2.^[16]

See also

• Transforming growth factor

References

Further reading

External links

• Transforming+Growth+Factor+alpha at the U.S. 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.