Part:BBa_K4040034

Truncated HER2

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  INCOMPATIBLE WITH RFC[21]

  Illegal BglII site found at 1040
  Illegal BamHI site found at 1235
  
• 23
  COMPATIBLE WITH RFC[23]
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal NgoMIV site found at 595
  Illegal NgoMIV site found at 658
  Illegal NgoMIV site found at 1027
  
• 1000
  INCOMPATIBLE WITH RFC[1000]

  Illegal BsaI.rc site found at 52
  Illegal BsaI.rc site found at 1135
  

Usage and Biology

HER2 is a protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. It is an essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. HER2 Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.

In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. It is implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC and is also involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.

Figure 1. The structure of HER2.

References

[1]Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE. ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J Biol Chem. 1999 Jun 11;274(24):17209-18. doi: 10.1074/jbc.274.24.17209. PMID: 10358079.

[2]Wang SC, Lien HC, Xia W, Chen IF, Lo HW, Wang Z, Ali-Seyed M, Lee DF, Bartholomeusz G, Ou-Yang F, Giri DK, Hung MC. Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2. Cancer Cell. 2004 Sep;6(3):251-61. doi: 10.1016/j.ccr.2004.07.012. PMID: 15380516.

[3]Li LY, Chen H, Hsieh YH, Wang YN, Chu HJ, Chen YH, Chen HY, Chien PJ, Ma HT, Tsai HC, Lai CC, Sher YP, Lien HC, Tsai CH, Hung MC. Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes. Cancer Res. 2011 Jun 15;71(12):4269-79. doi: 10.1158/0008-5472.CAN-10-3504. Epub 2011 May 9. PMID: 21555369; PMCID: PMC3117049.

2022 NMU_China

Usage supplementation:

HER2, also known as ErbB2, is one of four members (HER1–4) of the epidermal growth factor receptor or HER family. All HER receptors share a similar structure: an extracellular ligand-binding domain, a short hydrophobic transmembrane region, and a cytoplasmic tyrosine kinase domain . Hetero- or homodimerization of HER receptors, induced by ligand binding or receptor overexpression, leads to the activation of the receptor kinase and to the subsequent phosphorylation of several tyrosine residues. In turn, these phosphorylated tyrosine residues, located within the carboxyl terminus of the receptors, recruit mediators and activate signaling pathways that result in the modification of the cell growth, differentiation, and survival.

When referencing as truncated receptor, it is usually means the p95HER2, which has kinase activity in the absence of the trastuzumab-binding extracellular domain led us to hypothesize that p95HER2–expressing tumors may be resistant to trastuzumab but sensitive to the inhibitory effects of lapatinib, a low–molecular-weight tyrosine kinase inhibitor (TKI) of HER2 that has activity in patients with HER2–expressing tumors that are resistant to trastuzumab.

However, this parts includes the Truncated HER2 without the ICD domain, which can be used as a marker for engineered synthetic immune cells or other cells, such as CAR-T cells or liver cells. When used as a marker, the engineered cell can be easily cleared with anti-HER2 antibodies, such as Trastuzumab,or other HER2 targeting methods [1]

References

[1]Castellarin M, Sands C, Da T, et al. A rational mouse model to detect on-target, off-tumor CAR T cell toxicity[J]. JCI insight, 2020, 5(14).