CD148, a New Membrane Tyrosine Phosphatase Involved in Leukocyte Function

Gayà, Antoni; Pirotto, F; Palou, Eduard; Autschbach, Frank; Pozo, Victoria del; Sole, Josepa; Serra-Pagès, Carles

doi:10.3109/10428199909145726

Cited by 18 publications

(19 citation statements)

References 24 publications

(7 reference statements)

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“…CD148, also known as Ptprj or DEP-1, is a receptor-like protein tyrosine phos phatase (RPTP) that is comprised of an extracellular domain consisting of 8 fibronectin-type repeats, a transmembrane domain, and a cytoplasmic phosphatase domain. CD148 is highly expressed on both hematopoietic and nonhematopoietic cells, including cells of the lung (11)(12)(13). The physiologic function of CD148 outside of the hematopoietic system remains obscure, although it has been shown to be upregulated in epithelial cells grown at high density and has been implicated in regulating contact inhibition of cell growth.…”

Section: Introductionmentioning

confidence: 99%

The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases

Katsumoto¹,

Kudo²,

Chen³

et al. 2013

J. Clin. Invest.

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Increased airway smooth muscle (ASM) contractility and the development of airway hyperresponsiveness (AHR) are cardinal features of asthma, but the signaling pathways that promote these changes are poorly understood. Tyrosine phosphorylation is tightly regulated by the opposing actions of protein tyrosine kinases and phosphatases, but little is known about whether tyrosine phosphatases influence AHR. Here, we demonstrate that genetic inactivation of receptor-like protein tyrosine phosphatase J (Ptprj), which encodes CD148, protected mice from the development of increased AHR in two different asthma models. Surprisingly, CD148 deficiency minimally affected the inflammatory response to allergen, but significantly altered baseline pulmonary resistance. Mice specifically lacking CD148 in smooth muscle had decreased AHR, and the frequency of calcium oscillations in CD148-deficient ASM was substantially attenuated, suggesting that signaling pathway alterations may underlie ASM contractility. Biochemical analysis of CD148-deficient ASM revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SRC family kinases (SFKs), implicating CD148 as a critical positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM contractility could be mimicked by treatment of both mouse trachea and human bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR.

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Section: Introductionmentioning

confidence: 99%

The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases

Katsumoto¹,

Kudo²,

Chen³

et al. 2013

J. Clin. Invest.

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“…A few studies examining the expression of CD148 in human lymphocytes, especially T cells, have been published (1,10). These studies showed that CD148 is expressed at low levels on resting T cells, but is upregulated following activation (1,10).…”

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confidence: 99%

Regulated Expression of the Receptor-Like Tyrosine Phosphatase CD148 on Hemopoietic Cells

Lin

Zhu

Baker

et al. 2004

The Journal of Immunology

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CD148 is a receptor-like protein tyrosine phosphatase expressed on a wide variety of cell types. Through the use flow cytometry and immunofluorescence microscopy on tissue sections, we examined the expression of CD148 on multiple murine hemopoietic cell lineages. We found that CD148 is moderately expressed during all stages of B cell development in the bone marrow, as well as peripheral mature B cells. In contrast, CD148 expression on thymocytes and mature T cells is substantially lower. However, stimulation of peripheral T cells through the TCR leads to an increase of CD148 expression. This up-regulation on T cells can be partially inhibited by reagents that block the activity of src family kinases, calcineurin, MEK, or PI3K. Interestingly, CD148 levels are elevated on freshly isolated T cells from MRL lpr/lpr and CTLA-4-deficient mice, two murine models of autoimmunity. Together, these expression data along with previous biochemical data suggest that CD148 may play an important regulatory role to control an immune response.

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“…Less is known about CD148 expression on thymocytes. Immunohistochemical staining of human thymi revealed that CD148-positive T cells are localized in medulla, suggesting its expression in mature thymocytes (5,9). This was supported by flow cytometry that detected CD148 only on CD3-positive thymocytes (5).…”

mentioning

confidence: 54%

“…Moreover, murine thymocytes were almost CD148-negative with a weak signal only at early stages (10). In contrast, the limited data available on human thymi suggested that the regulation of CD148 expression on human thymocytes may be very different, with CD148 expression appearing at the later stages of T cell development (5,9). However, no detailed subset analysis has been carried out.…”

Section: Cd148 Is Differentially Expressed On Human and Murine Tmentioning

confidence: 95%

Regulation of Src Family Kinases Involved in T Cell Receptor Signaling by Protein-tyrosine Phosphatase CD148

Štěpánek

Kalina

Dráber

et al. 2011

Journal of Biological Chemistry

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CD148 is a receptor-like protein-tyrosine phosphatase known to inhibit transduction of mitogenic signals in non-hematopoietic cells. Similarly, in the hematopoietic lineage, CD148 inhibited signal transduction downstream of T cell receptor. However, it also augmented immunoreceptor signaling in B cells and macrophages via dephosphorylating C-terminal tyrosine of Src family kinases (SFK). Accordingly, endogenous CD148 compensated for the loss of the main SFK activator CD45 in murine B cells and macrophages but not in T cells. Hypothetical explanations for the difference between T cells and other leukocyte lineages include the inability of CD148 to dephosphorylate a specific set of SFKs involved in T cell activation or the lack of CD148 expression during critical stages of T cell development. Here we describe striking differences in CD148 expression between human and murine thymocyte subsets, the only unifying feature being the absence of CD148 during the positive selection when the major developmental block occurs under CD45 deficiency. Moreover, we demonstrate that similar to CD45, CD148 has both activating and inhibitory effects on the SFKs involved in TCR signaling. However, in the absence of CD45, activating effects prevail, resulting in functional complementation of CD45 deficiency in human T cell lines. Importantly, this is independent of the tyrosines in the CD148 C-terminal tail, contradicting the recently proposed phosphotyrosine displacement model as a mechanism of SFK activation by CD148. Collectively, our data suggest that differential effects of CD148 in T cells and other leukocyte subsets cannot be explained by the CD148 inability to activate T cell SFKs but rather by its dual inhibitory/ activatory function and specific expression pattern.

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CD148, a New Membrane Tyrosine Phosphatase Involved in Leukocyte Function

Cited by 18 publications

References 24 publications

The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases

The phosphatase CD148 promotes airway hyperresponsiveness through SRC family kinases

Regulated Expression of the Receptor-Like Tyrosine Phosphatase CD148 on Hemopoietic Cells

Regulation of Src Family Kinases Involved in T Cell Receptor Signaling by Protein-tyrosine Phosphatase CD148

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