Protein-Tyrosine Phosphatases Expressed in Mouse Epidermal Keratinocytes

Hendriks, Wiljan; Brugman, C.; Richter, Karsten; Hooijdonk, C.A.E.M. van; Schepens, Jan; Schalkwijk, Joost; Wieringa, Bé

doi:10.1111/1523-1747.ep12338472

Cited by 10 publications

(11 citation statements)

References 38 publications

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“…data]. Both of these PTPs are known to be expressed in mouse epidermal keratinocytes [Hendriks et al, 1996] and normal human skin [Nanney et al, 1997]. In HaCaT cells, the localization of PTP1B was confined to the perinuclear cytoplasm (i.e.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor-, Transforming Growth Factor-β-, Retinoic Acid- and 1,25-Dihydroxyvitamin D<sub>3</sub>-Regulated Expression of the Novel Protein PTPIP51 in Keratinocytes

Schreiner

Pfeiffer

Tag

et al. 2006

Cells Tissues Organs

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The novel protein PTPIP51 (protein tyrosine phosphatase-interacting protein 51), which has been found to interact with protein tyrosine phosphatases of the PTP1B/TcPTP subfamily, is expressed in all suprabasal layers of human epidermis. Hence, a human keratinocyte cell line (HaCaT) grown on culture slides was used as a simplified model system to study the influence of hormonal agents on the regulation of PTPIP51 expression. Results were obtained by immunocytochemistry and subsequent statistical analysis. Additionally, immunoblotting was performed to detect the possible occurrence of distinct molecular weight forms as described previously. Subcellular localization of PTPIP51 protein was analyzed by specific staining of cellular organelles. HaCaT cells were subjected to treatment with factors that are crucial for the regulation of proliferation and differentiation of keratinocytes in human epidermis: epidermal growth factor (EGF), transforming growth factor-β(TGF-β), retinoic acid (RA) and 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃]. Epidermal growth factor receptor (EGFR) expressed in HaCaT cells was inhibited by PD153035. Only about 35% of untreated HaCaT cells were immunoreactive for the PTPIP51 protein. Whereas cells treated with increasing concentrations of 1,25 (OH)₂D₃ showed a stepwise numerical increase of PTPIP51-positive cells, treatment with RA did not influence the number of PTPIP51-positive cells except when supraphysiological concentrations were applied. Concentration-dependent increase of cells stained positive for PTPIP51 was also observed when HaCaT cells were subjected to EGF treatment. Additional treatment of these cells with PD153035 led to a slight decrease in the fraction of PTPIP51-positive cells, which was not statistically significant. Immunoblotting results suggest a specific pattern of different molecular weight forms of PTPIP51 being expressed in HaCaT cells. Subcellular analysis revealed an association of the protein with mitochondria in nonconfluent cells, whereas confluent cells lack such correlation. The intracellular distribution of PTPIP51 resembled the localization of its interacting partner TcPTP. Furthermore, PTPIP51 was found to be present in both the nucleus and cytoplasm of HaCaT cells. In summary, the results indicate a possible association of PTPIP51 expression with differentiation as well as with apoptosis of keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor-, Transforming Growth Factor-β-, Retinoic Acid- and 1,25-Dihydroxyvitamin D<sub>3</sub>-Regulated Expression of the Novel Protein PTPIP51 in Keratinocytes

Schreiner

Pfeiffer

Tag

et al. 2006

Cells Tissues Organs

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“…The maturation includes the formation of a cornified envelope, the loss of the nucleus, the elimination of the plasma membrane and keratinisation [2]. The cell transformations occurring during the differentiation of the keratinocytes are activated and controlled by kinases and phosphatases [3]. In fact, these enzymes are part of a group that not only performs a kinase regulation function but which is also involved in other functions, in particular, the transformation of profilaggrins into filaggrins, enhancing the association of keratins to form macrofilaments in the stratum granulosum [4].…”

Section: Introductionmentioning

confidence: 99%

Characterisation and Assay of Five Enzymatic Activities in the Stratum Corneum Using Tape-Strippings

Redoulès

Tarroux

Assalit

et al. 1999

Skin Pharmacol Physiol

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The report describes a method for the assay of five enzymatic activities involved in establishing the stratum corneum permeability barrier: β-glucocerebrosidase, acid phosphatase, phospholipase A₂ (PLA₂) and two serine proteases: chymotrypsin and its activator in the stratum corneum, trypsin. The specific activities of these different enzymes have been determined along with their pH profiles and sensivities to specific inhibitors. It can be noted that only two presented a pH optimum similar to the pH of the stratum corneum. This could suggest that their activities are regulated by local variations in pH. The method was applied to a pathological situation, that of a non-eczematous dry atopic dermatitis. Atopic skin had significantly reduced trypsin activity, increased acid phosphatase and no change in the activities of three other studied enzymes. Understanding these activities can provide a tool for the characterization of skin pathologies and for the development of a certain number of applications in cosmetology and therapeutics.

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“…Initial studies of PTPs in skin showed that despite the fact that PTP expression is induced during keratinocyte proliferation and maturation, their expression levels remain unchanged within epidermal tissue14. Exposure to acute ultraviolet (UV) irradiation or treatment with the tumor promoter, 12- O -tetradecanoylphorbol-13-acetate (TPA), increases the activation of PTKs including the epidermal growth factor receptor (EGFR) and the downstream STAT3 signaling pathway151617181920.…”

mentioning

confidence: 99%

Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development

Lee

Kim

Baek

et al. 2017

Sci Rep

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Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2fl/fl) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP deficiency also resulted in a significant increase in epidermal thickness and hyperproliferation following exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis showed that both phosphorylated STAT3 and phosphorylated AKT expressions were significantly increased in epidermis of TC-PTP-deficient mice compared to control mice following TPA treatment. Inhibition of STAT3 or AKT reversed the effects of TC-PTP deficiency on apoptosis and proliferation. Finally, TC-PTP knockout mice showed a shortened latency of tumorigenesis and significantly increased numbers of tumors during two-stage skin carcinogenesis. Our findings reveal that TC-PTP has potential as a novel target for the prevention of skin cancer through its role in the regulation of STAT3 and AKT signaling.

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Protein-Tyrosine Phosphatases Expressed in Mouse Epidermal Keratinocytes

Cited by 10 publications

References 38 publications

Epidermal Growth Factor-, Transforming Growth Factor-β-, Retinoic Acid- and 1,25-Dihydroxyvitamin D<sub>3</sub>-Regulated Expression of the Novel Protein PTPIP51 in Keratinocytes

Epidermal Growth Factor-, Transforming Growth Factor-β-, Retinoic Acid- and 1,25-Dihydroxyvitamin D<sub>3</sub>-Regulated Expression of the Novel Protein PTPIP51 in Keratinocytes

Characterisation and Assay of Five Enzymatic Activities in the Stratum Corneum Using Tape-Strippings

Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development

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