title: Cellular signaling by tyrosine phosphorylation in keloid and normal human dermal fibroblasts.
abstract: Keloids represent a dysregulated response to cutaneous wounding that results in disfiguring scars. Unique to humans, keloids are characterized by an accumulation of extracellular matrix components. The underlying molecular mechanisms of keloid pathogenesis, however, remain largely uncharacterized. Similarly, cellular signaling mechanisms, which may indicate inherent differences in the way keloid fibroblasts and normal human dermal fibroblasts interact with extracellular matrix or other cells, have not been investigated. As part of a fundamental assessment of cellular response to injury in keloid fibroblasts, phosphorylation studies were performed using three different keloid (n = 3) and normal human dermal (n = 3) fibroblast cell lines. These studies were undertaken to elucidate whether keloid and normal human dermal fibroblasts exhibit different tyrosine kinase activity. Initially, distinct tyrosine phosphorylation patterns of keloid and normal human dermal fibroblasts were demonstrated. Next, the phosphorylation patterns were correlated with known molecules that may be important to keloid pathogenesis. On the basis of molecular weight, it was hypothesized that the highly phosphorylated bands seen in keloid fibroblasts represented epidermal growth factor receptor (EGFR); discoidin domain receptor 1 (DDR1); and Shc, an adaptor protein known to bind many tyrosine kinases, including EGFR and DDR1. Individual immunoblotting using EGFR, DDR1, and Shc antibodies revealed greater expression in keloid fibroblasts compared with normal human dermal fibroblasts. These data substantiate for the first time the finding of greater phosphorylation by the above-mentioned molecules, which may be important in keloid pathogenesis.
authors: Department of Surgery, New York University Medical Center, New York, USA.
authors: G S
authors: GS
authors: Chin
authors: W
authors: W
authors: Liu
authors: D
authors: D
authors: Steinbrech
authors: M
authors: M
authors: Hsu
authors: H
authors: H
authors: Levinson
authors: M T
authors: MT
authors: Longaker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000293:Adolescent; D000328:Adult; D000906:Antibodies; D015153:Blotting, Western; D002460:Cell Line; D000070818:Discoidin Domain Receptors; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007627:Keloid / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D008970:Molecular Weight; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000032:analysis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D011975:Receptors, Mitogen / Q000032:analysis / Q000235:genetics; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000906:Antibodies; D011506:Proteins; D011975:Receptors, Mitogen; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019000:Phosphotyrosine; D000070818:Discoidin Domain Receptors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases