Her2orERBB2belongstoaclassofproteinshavinghighhomologywithepidermalgrowthfactorreceptor(EGFRorERBB1).Itencodesaproteinwiththemolecularweightof185KDa.UnlikeothermembersofEGFRfamily,noligandforHer2hasbeenfoundanditusuallyassociateswithmembersofERBB1familytoformfunctionalheterodimers.IthasbeenshownthatitcanformdimerswithERBB(EGFR),ERBB3andERBB4aswellasgp130subunitsofIL-6receptor.Inatleastsomecelltypes,theassociationbetweengp130andHRBB2isessentialforHRBB2-ERBB3phosphorylationandsubsequentMAPkinasesignaling.AlthoughERBB1canformhomodimers,thesignalingforERBB1isusuallytransientandthereceptorundergoesinternalizationafterligandbindingandactivation.EGFR-HER2complexincreasesthesignalingcapacityofEGFRbyincreasingtheligandaffinityaswellastherecyclingoftheheterodimer.OfalltheERBBheterodimers,ERBB2-ERBB3heterodimersperhapselicitthestrongestsignal.RemovingERBB3fromthecellhasadrasticeffectonERBB2mediatedsignalinganddownstreameffectors.TheclinicalimportanceofHER2cannotbeoverstated.Inaddition,monoclonalantibody(Herceptin)againstthisreceptorhasbeenshowntobeaneffectivetreatmentofbreastcancerpatientswhohaveahighlevelofHER2overexpression.

Contributor:Yen-LiangChen,PhD

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