Phospho-EGFR (S695) Recombinant Rabbit Monoclonal Antibody [SN07-36]

Function

The EGF receptor family comprises several related receptor tyrosine kinases that are frequently overexpressed in a variety of carcinomas. Members of this receptor family include EGFR (HER1), Neu (ErbB-2, HER2), ErbB-3 (HER3) and ErbB-4 (HER4), which form either homodimers or heterodimers upon ligand binding. Exons in the EGFR gene product are frequently either deleted or duplicated to produce deletion mutants (DM) or tandem duplication mutants (TDM), respectively, which are detected at various molecular weights. EGFR binds several ligands, including epidermal growth factor (EGF), transforming growth factor α (TGFα), Amphiregulin and heparin binding-EGF (HB-EGF). Ligand binding promotes the internalization of EGFR via Clathrin-coated pits and its subsequent degradation in response to its intrinsic tyrosine kinase. EGFR is involved in organ morphogenesis and maintenance and repair of tissues, but upregulation of EGFR is associated with tumor progression. The oncogenic effects of EGFR include initiation of DNA synthesis, enhanced cell growth, invasion and metastasis. Abrogation of EGFR results in cell cycle arrest, apoptosis or dedifferentiation of cancer cells, suggesting that EGFR may be an effective therapeutic target.

Background References

1. Chen CC et al. The matricellular protein CCN1 suppresses hepatocarcinogenesis by inhibiting compensatory proliferation. Oncogene 35:1314-23 (2016).

2. Shuai S et al. TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma. Cancer Lett 354:200-9 (2014).

Sequence Similarity

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Tissue Specificity

Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers.

Post-translational Modification

Phosphorylated on Tyr residues in response to EGF. Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Dephosphorylated by PTPN1 and PTPN2.; Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitination by OTUD7B prevents degradation. Ubiquitinated by RNF115 and RNF126 (By similarity).; Palmitoylated on Cys residues by ZDHHC20. Palmitoylation inhibits internalization after ligand binding, and increases the persistence of tyrosine-phosphorylated EGFR at the cell membrane. Palmitoylation increases the amplitude and duration of EGFR signaling.; Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.

Subcellular Location

Cell membrane, Nucleus, Endoplasmic reticulum membrane, Golgi apparatus membrane, Endosome, Secreted.

UNIPROT

SwissProt: P00533 Human

Synonyms