Erbb2

Function

Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. 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 (By similarity). Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner (By similarity).

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. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth (By similarity).

Post-translational modifications

Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligand-binding increases phosphorylation on tyrosine residues. Signaling via SEMA4C promotes phosphorylation at Tyr-1250. Dephosphorylated by PTPN12.

Sequence Similarities

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

Cellular localization

• Cell membrane
• Single-pass type I membrane protein
• Cell projection
• Ruffle membrane
• Single-pass type I membrane protein
• Early endosome
• Cytoplasm
• Perinuclear region
• Nucleus
• Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1. Also detected in endosome-to-TGN retrograde vesicles. Internalized from the cell membrane in response to EGF stimulation.

Alternative names

CD340, Neu, Erbb2, Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor-related protein, Proto-oncogene Neu, Proto-oncogene c-ErbB-2, p185erbB2, p185neu

Database links

swissprot:P06494 entrezGene:24337

Other research areas

• Immuno-oncology