title: Regulation of hemidesmosome disassembly by growth factor receptors.
abstract: Hemidesmosomes (HDs) promote the stable adhesion of basal epithelial cells to the underlying basement membrane (BM). Critical for the mechanical stability of the HD is the interaction between integrin alpha6beta4 and plectin, which is destabilized when HD disassembly is required, for instance, to allow keratinocyte migration during wound healing. Growth factors such as epidermal growth factor (EGF) can trigger HD disassembly and induce phosphorylation of the beta4 intracellular domain. Whereas tyrosine phosphorylation appears to mediate cooperation with growth factor signaling pathways and invasion in carcinoma cells, serine phosphorylation seems the predominant mechanism for regulating HD destabilization. Here, we discuss recent advances that shed light on the residues involved, the identity of the kinases that phosphorylate them, and the interactions that become disrupted by these phosphorylations.
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Coert
authors.initials: C
authors.lastname: Margadant
authors.forename: Evelyne
authors.initials: E
authors.lastname: Frijns
authors.forename: Kevin
authors.initials: K
authors.lastname: Wilhelmsen
authors.forename: Arnoud
authors.initials: A
authors.lastname: Sonnenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D022002:Hemidesmosomes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D039161:Integrin alpha6beta4 / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D051190:Plectin / Q000737:chemistry / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D039161:Integrin alpha6beta4; D051190:Plectin; D017978:Receptors, Growth Factor; D014443:Tyrosine; D012694:Serine