Background of the antigen
ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ErbB3 is a membrane-bound protein which has a neuregulin binding domain but not an active kinase domain. It can therefore bind this ligand but cannot convey a signal into the cell via protein phosphorylation. However it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers including prostate, bladder and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. Isoform 2 lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported but they have not been thoroughly characterized. Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2); also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord.
