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TGFBR2

MIM.190182 3p22

Monday 3 September 2007

Function

Growth factor-induced protein phosphorylation plays a key role in the signal transduction that leads to mitogenic responses.

Most growth factor receptors are transmembrane tyrosine kinases or are associated with cytoplasmic tyrosine kinases. However, another class of transmembrane receptors is predicted to function as serine-threonine kinases. The type II activin receptor (MIM.102581) and the types I (MIM.190181) and II TGF-beta receptors belong to the serine-threonine kinase family.

The many activities of TGF-beta (TGFB1) (MIM.190180) in regulating cell proliferation and differentiation and extracellular matrix production are mediated through these receptors.

The type I receptors are responsible for effects on extracellular matrix, such as the induction of fibronectin and plasminogen activator inhibitor I, and for increased JUNB (MIM.165161) expression.

The type II receptors, possibly in conjunction with type I receptors, mediate the induction of growth inhibition and hypophosphorylation of the retinoblastoma gene product.

Selective inactivation of the type II receptors alters the response to TGF-beta in a manner similar to the functional inactivation of the RB protein, suggesting a role for RB in the type II, but not the type I, receptor pathway.

Pathology

The implication of mutations in the TGFBR2 gene, known to be involved in cancers, in Marfan syndrome (MFS), in Loeys-Dietz syndrome (LDS) and Familial Thoracic Aortic Aneurysms and Dissections (TAAD2) gives a new example of the complexity of one gene involved in multiple diseases.

- germline mutations of TGFBR2

- somatic mutations of TGFBR2 in

  • exophageal carcinoma

- Mutated TGFBR2 seems to play an important role in the abrogation of TGFB signal transduction in tumoral cells.

See also

- DNA mismatch repair
- HNPCCs

Open references

- Heterozygous TGFBR2 mutations in Marfan syndrome. Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, Allard D, Varret M, Claustres M, Morisaki H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Jondeau G, Ohta T, Kishino T, Furukawa Y, Nakamura Y, Niikawa N, Boileau C, Matsumoto N. Nat Genet. 2004 Aug;36(8):855-60. PMID: 15235604 [Free]

References

- Wang JC, Su CC, Xu JB, Chen LZ, Hu XH, Wang GY, Bao Y, Huang Q, Fu SB, Li P, Lu CQ, Zhang RM, Luo ZW. Novel microdeletion in the transforming growth factor beta type II receptor gene is associated with giant and large cell variants of nonsmall cell lung carcinoma. Genes Chromosomes Cancer. 2007 Feb;46(2):192-201. PMID: 17117417