Membrane‐anchored growth factors, the epidermal growth factor family: Beyond receptor ligands

Higashiyama, Shigeki; Iwabuki, Hidehiko; Morimoto, Chie; Hieda, Miki; Inoue, Hirofumi; Matsushita, Natsuki

doi:10.1111/j.1349-7006.2007.00676.x

Cited by 191 publications

(189 citation statements)

References 117 publications

(172 reference statements)

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“…Wounding sheets of corneal epithelial cells causes release of heparin-binding EGF-like growth factor and amphiregulin (19,20,22,32). Both of these ligands bind strongly to negatively charged glycans in the extracellular matrix and the cell surface (56)(57)(58). This limits their diffusion and provides an explanation why the receptor is activated only very locally.…”

Section: Discussionmentioning

confidence: 99%

Dual modes of motility at the leading edge of migrating epithelial cell sheets

Klarlund

2012

Proc. Natl. Acad. Sci. U.S.A.

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Purse-string healing is driven by contraction of actin/myosin cables that span cells at wound edges, and it is the predominant mode of closing small round wounds in embryonic and some adult epithelia. Wounds can also heal by cell crawling, and my colleagues and I have shown previously that the presence of unconstrained, straight edges in sheets of epithelial cells is a sufficient signal to induce healing by crawling. Here, it is reported that the presence of highly concave edges, which are free or physically constrained by an inert material (agarose), is sufficient to induce formation of purse strings. It was determined that neither of the two types of healing required cell damage or other potential stimuli by using the particularly gentle procedure of introducing gaps by digesting agarose blocks imbedded in the cell sheets. Movement by crawling depends on signaling by the EGF receptor (EGFR); however, this was not required for purse-string contraction. A migrating epithelial cell sheet usually produces finger-like projections of crawling cells. The cells between fingers contain continuous actin cables, which were also determined to contain myosin IIA and exhibit additional characteristics of purse strings. When crawling was blocked by inhibition of EGFR signaling, the concave regions continued to move, suggesting that both mechanisms contribute to propel the sheets forward. Wounding epithelial cell sheets causes activation of the EGFR, which triggers movement by crawling. The EGFR was found to be activated only at straight and convex edges, which explains how both types of movement can coexist at leading epithelial edges.

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Section: Discussionmentioning

confidence: 99%

Dual modes of motility at the leading edge of migrating epithelial cell sheets

Klarlund

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…15,24 These factors are synthesized as type I transmembrane proteins that are post-translationally processed into soluble factors by proteases, such as the disintegrin and metalloproteases (ADAMs), in a process known as ectodomain shedding, and they are then free to act as autocrine or paracrine growth factors. 25 The EGF-family ligands bind to a group of four homo-or heterodimeric RTKs: HER1 (commonly known as EGFR, ErbB-1), HER2 (Neu, ErbB-2), HER3 (ErbB-3), and HER4 (ErbB-4). These receptors can be broadly subdivided into two groups based on their ligand specificities: HER1 binds all EGF-family ligands except the neuregulins, whereas HER2, 3, and 4 bind the neuregulins in addition to other select EGF-family ligands.…”

Section: 21mentioning

confidence: 99%

The Roles of Growth Factors in Keratinocyte Migration

Seeger

Paller

2015

Advances in Wound Care

169

126

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“…Importantly, shedding of EGFR ligands by ADAMs not only yields extracellular ligand but an intracellular carboxylterminal fragment that is functionally relevant, resulting in independent signalling. This remnant peptide may translocate to the inner nuclear membrane and regulate gene expression (Higashiyama et al, 2008). The importance of carboxyl-terminal fragment signalling to cardioprotection has yet to be examined.…”

Section: Mechanisms Of Egfr Transactivationmentioning

confidence: 99%