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Gene Review

SHC3  -  SHC (Src homology 2 domain containing)...

Homo sapiens

Synonyms: N-Shc, NSHC, Neuronal Shc, Protein Rai, RAI, ...
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Disease relevance of SHC3

  • Analysis of the phosphorylation status of Shc3 in human glioblastoma tumor samples in vivo indicates that it is tyrosine phosphorylated [1].
  • Shc3 affects human high-grade astrocytomas survival [1].
  • Finally, we found that the expression of truncated variants of Shc3 with dominant-negative effects in human high-grade glioma cells that maintain Shc3 expression in vitro leads to a decreased Akt posphorylation and increased apoptosis, thus resulting in impaired survival of the transfected cells [1].
  • METHODS: Hepatocellular carcinomas (HCC) from 31 cases were divided into small HCC (SHCC), nodular HCC (NHCC) and solitary large HCC (SLHCC) according to tumor diameter and the number of nodes [2].
  • The incidences of tumor capsule breaking and cancerous thrombosis were 16% and 20% respectively in SHCC, significantly lower than 84% and 80% in LHCC (P less than 0.01) [3].

High impact information on SHC3

  • Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases [4].
  • In the peripheral nervous system, transcripts of Shc and Sck, but not of N-Shc, were detected [5].
  • RAI, also named ShcC/N-Shc, one of the members of the Shc proteins family, is a substrate of the RET receptor tyrosine kinase [6].
  • Under normal conditions Shc3 is never expressed by glial cells [1].
  • Previous studies showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is silenced in mature neurons, where it is replaced by Shc3 [1].

Associations of SHC3 with chemical compounds

  • As further support, we found that nicotine administered through infusion increased the Shc3 mRNA level by 60% in the rat striatum, and decreased it by 22% in the nucleus accumbens (NA) [7].

Biological context of SHC3


  1. Shc3 affects human high-grade astrocytomas survival. Magrassi, L., Conti, L., Lanterna, A., Zuccato, C., Marchionni, M., Cassini, P., Arienta, C., Cattaneo, E. Oncogene (2005) [Pubmed]
  2. ADAM17 mRNA expression and pathological features of hepatocellular carcinoma. Ding, X., Yang, L.Y., Huang, G.W., Wang, W., Lu, W.Q. World J. Gastroenterol. (2004) [Pubmed]
  3. Small hepatocellular carcinoma. DNA content and biological characteristics. Cong, W.M., Wu, M.C. Chin. Med. J. (1989) [Pubmed]
  4. Grit, a GTPase-activating protein for the Rho family, regulates neurite extension through association with the TrkA receptor and N-Shc and CrkL/Crk adapter molecules. Nakamura, T., Komiya, M., Sone, K., Hirose, E., Gotoh, N., Morii, H., Ohta, Y., Mori, N. Mol. Cell. Biol. (2002) [Pubmed]
  5. N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their differential regional expression in the brain and roles in neurotrophin and Src signaling. Nakamura, T., Muraoka, S., Sanokawa, R., Mori, N. J. Biol. Chem. (1998) [Pubmed]
  6. RAI(ShcC/N-Shc)-dependent recruitment of GAB 1 to RET oncoproteins potentiates PI 3-K signalling in thyroid tumors. De Falco, V., Guarino, V., Malorni, L., Cirafici, A.M., Troglio, F., Erreni, M., Pelicci, G., Santoro, M., Melillo, R.M. Oncogene (2005) [Pubmed]
  7. Linkage and association studies in African- and Caucasian-American populations demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence. Li, M.D., Sun, D., Lou, X.Y., Beuten, J., Payne, T.J., Ma, J.Z. Mol. Psychiatry (2007) [Pubmed]
  8. Molecular cloning of EDG-3 and N-Shc genes from the puffer fish, Fugu rubripes, and conservation of synteny with the human genome. Yamaguchi, F., Yamaguchi, K., Tokuda, M., Brenner, S. FEBS Lett. (1999) [Pubmed]
  9. A human SHC-related sequence maps to chromosome 17, the SHC gene maps to chromosome 1. Yulug, I.G., Egan, S.E., See, C.G., Fisher, E.M. Hum. Genet. (1995) [Pubmed]
  10. The biopathologic characteristics of DNA content of hepatocellular carcinomas. Cong, W.M., Wu, M.C. Cancer (1990) [Pubmed]
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