The rat tyrosine phosphatase η increases cell adhesion by activating c-Src through dephosphorylation of its inhibitory phosphotyrosine residue

Pera, Ilaria Le; Iuliano, Rodolfo; Florio, Tullio; Susini, Christiane; Trapasso, Francesco; Santoro, Massimo; Chiariotti, Lorenzo; Schettini, Gennaro; Viglietto, Giuseppe; Fusco, Alfredo

doi:10.1038/sj.onc.1208510

Cited by 46 publications

(60 citation statements)

References 46 publications

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“…Moreover, we bring evidence that in addition to the C-terminal inhibitory phosphotyrosine, the activation loop phosphotyrosine in SFKs is also a substrate of CD148 in living cells. This finding is also supported by previous observations that recombinant CD148 phosphatase domain dephosphorylated activation loop tyrosines in SFKs in vitro (23,48).…”

Section: Discussionsupporting

confidence: 80%

“…CD148 has been previously shown to play a positive role in surface receptor signal transduction via dephosphorylation of inhibitory tyrosines of SFKs in B cells, macrophages, platelets, and some non-hematopoietic tissues (19,(23)(24)(25). On the other hand, CD148 has been reported to act as a negative regulator of signal transduction in many non-hematopoietic biological systems as well as in TCR signaling in human T cell line Jurkat (29 -31).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, CD148 also plays an activating role via dephosphorylation of the inhibitory tyrosine in Src (19,23).…”

Section: Cd4mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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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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“…For histology, sections were stained using Movat's pentachrome [28]. Tartrate resistant acid phosphatase [29] staining procedure was previously described [30]. For Cre immunohistochemistry, tissue sections were permeabilized with cold acetone for 10 min followed by overnight incubation with the primary antibody.…”

Section: Histology Immunohistochemistry and Whole Mount Skeletal Stamentioning

confidence: 99%

Reconciling the roles of FAK in osteoblast differentiation, osteoclast remodeling, and bone regeneration

Kim

Leucht

Luppen

et al. 2007

Bone

104

116

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Integrins link the inside of a cell with its outside environment and in doing so regulate a wide variety of cell behaviors. Integrins are well known for their roles in angiogenesis and cell migration but their functions in bone formation are less clear. The majority of integrin signaling proceeds through focal adhesion kinase (FAK), an essential component of the focal adhesion complex. We generated transgenic mice in which FAK was deleted in osteoblasts and uncovered a previously unknown role in osteoblast differentiation associated with bone healing. FAK mutant cells migrated to the site of skeletal injury and angiogenesis was unaffected yet the transgenic mice still exhibited numerous defects in reparative bone formation. Osteoblast differentiation itself was unperturbed by the loss of FAK, whereas the attachment of osteoclasts to bone matrix was disrupted in vivo. We postulate that defective bi-directional integrin signaling affects the organization of the collagen matrix. Finally, we present a compensatory candidate molecule, Pyk2, which localized to the focal adhesions in osteoblasts that were lacking FAK.

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“…In agreement, dephosphorylation of the C-terminal tyrosine by tyrosine phosphatases (PTPs) activates c-Src. PTPs known to perform this role include PTP1B, SHP1, SHP2, DEP-1, CD45, RPTPa, PTPe and PTPRO (Mustelin and Hunter, 2002;Gil-Henn and Elson, 2003;Pera et al, 2005;Roskoski, 2005;Lau et al, 2006). Of these, the molecular details concerning RPTPa are the most complete.…”

Section: Introductionmentioning

confidence: 99%

Neu-mediated phosphorylation of protein tyrosine phosphatase epsilon is critical for activation of Src in mammary tumor cells

Berman-Golan

Elson

2007

Oncogene

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The receptor-type protein tyrosine phosphatase epsilon (RPTPe) activates c-Src in mammary tumor cells induced in vivo by Neu. Tumor cells lacking RPTPe exhibit reduced c-Src activity, appear less transformed morphologically and proliferate slower in vitro and in vivo. Expression of Src rescues most of these phenotypes, indicating that c-Src activity is important for maintaining the transformed phenotype. However, the molecular mechanisms that control activation of c-Src by RPTPe are unknown. We show that Neu induces phosphorylation of RPTPe exclusively at its C-terminal Y695, and that this phosphorylation is required for activation of c-Src by RPTPe. Phosphorylation of RPTPe does not affect its activity toward another substrate, the voltage-gated potassium channel Kv2.1, suggesting that phosphorylation directs RPTPe activity toward c-Src. Phosphorylation of RPTPe reduces its dimerization at the cell membrane, although this does not affect its activity significantly. RPTPe is subject to strong auto-and trans-dephosphorylation, suggesting that dephosphorylation limits the activation of c-Src downstream of Neu. We conclude that an Neu-RPTPe-Src signaling pathway exists in mammary tumor cells, in which phosphorylation of RPTPe by Neu directs RPTPe to activate c-Src. Reversible phosphorylation of RPTPe at Y695 may thus function as a 'molecular switch', which affects the substrate specificity of the phosphatase.

show abstract

The rat tyrosine phosphatase η increases cell adhesion by activating c-Src through dephosphorylation of its inhibitory phosphotyrosine residue

Cited by 46 publications

References 46 publications

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

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

Reconciling the roles of FAK in osteoblast differentiation, osteoclast remodeling, and bone regeneration

Neu-mediated phosphorylation of protein tyrosine phosphatase epsilon is critical for activation of Src in mammary tumor cells

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