2018
DOI: 10.1038/s41419-018-0509-x
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Role of FGFR2b expression and signaling in keratinocyte differentiation: sequential involvement of PKCδ and PKCα

Abstract: The tumor suppressor epithelial isoform of the fibroblast growth factor receptor 2 (FGFR2b) induces human keratinocyte early differentiation. Moreover, protein kinases C (PKCs) are known to regulate the differentiation program in several cellular contexts, including keratinocytes. Therefore, in this paper we propose to clarify if FGFR2b could play a role also in the late steps of keratinocyte differentiation and to assess if this receptor-induced process would sequentially involve PKCδ and PKCα isoforms. Immun… Show more

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Cited by 18 publications
(18 citation statements)
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“…The phosphorylation of PKCδ at the autophosphorylation site Serine 645, which belongs to the characteristic phosphorylation pattern of PKCδ activation [19] was observed in all clones only in response to FGF7 (Fig. 1a), was in agreement with our recent data proposing a key role of this PKC family member in the early steps of FGF7-mediated keratinocyte differentiation [7]. No evident modulation of both PKCδ protein ( Fig.…”
Section: Pkcε Signaling Is Responsible For Fgfr2c-mediated Modulationsupporting
confidence: 91%
See 1 more Smart Citation
“…The phosphorylation of PKCδ at the autophosphorylation site Serine 645, which belongs to the characteristic phosphorylation pattern of PKCδ activation [19] was observed in all clones only in response to FGF7 (Fig. 1a), was in agreement with our recent data proposing a key role of this PKC family member in the early steps of FGF7-mediated keratinocyte differentiation [7]. No evident modulation of both PKCδ protein ( Fig.…”
Section: Pkcε Signaling Is Responsible For Fgfr2c-mediated Modulationsupporting
confidence: 91%
“…In this regard, several studies have demonstrated that the switching from the epithelial isoforms of fibroblast growth factor receptors (FGFR1-3b) to the mesenchymal FGFR1-3c isoforms is frequently involved in epithelialmesenchymal transition (EMT) and cancer progression [2][3][4]. In the last years we focused our attention on the biological functions of the epithelial FGFR2b isoform, demonstrating that this receptor controls the entire program of keratinocyte differentiation [5][6][7] through the sequential involvement of PKCδ and PKCα signaling [7]. In contrast, we found that the FGFR2 isoform switch and the aberrant expression of the mesenchymal FGFR2c isoform in the same epidermal context induced changes in FGFR ligand specificity, leading to impairment of differentiation [8], EMT and early tumorigenic features [9,10].…”
Section: Introductionmentioning
confidence: 99%
“…Concerning Fibroblast Growth Factor Receptors (FGFRs), several findings strongly suggested that the dysregulation of FGFR expression and signaling could also contribute to AK pathogenesis [ 10 , 11 , 12 ]. This possibility is also sustained by our recent observations, demonstrating that, while the epithelial isoform of FGFR2 (FGFR2b) is directly implicated in keratinocyte differentiation [ 13 ], the altered FGFR2 isoform switching and the consequent aberrant expression of the mesenchymal FGFR2c isoform in human keratinocytes induce changes in FGF specificity, leading to impairment of differentiation [ 14 ] and induction of EMT and tumorigenic features [ 15 , 16 ]. Even if our findings are consistent with the opposite oncogenic and tumor-suppressive roles previously proposed for FGFR2c and FGFR2b, respectively [ 17 , 18 , 19 ], the specific function of each FGFR2 isoform in carcinogenesis, and in particular their role during the progression of pre-malignant lesions, such as AK, remains to be further clarified.…”
Section: Introductionmentioning
confidence: 69%
“…In this regard, the epithelial isoform of FGFR2 (FGFR2b) is a well-recognized regulator of epidermal differentiation and skin homeostasis [5,6,7] exerting a tumor suppressive role in vitro and in vivo [8,9]. According to these studies, our group has demonstrated that FGFR2b controls the entire program of human keratinocyte differentiation [10,11,12] and that PKCδ and PKCα signaling downstream FGFR2b are involved in different steps of this process [12]. However, we also found that, in the same epidermal tissue context, the altered FGFR2 splicing and the aberrant expression of the mesenchymal FGFR2c isoform induces changes in the specificity for FGFs, leading to impairment of differentiation [13], epithelial mesenchymal transition (EMT) and early tumorigenic features [14].…”
Section: Introductionmentioning
confidence: 99%