The Lck Tyrosine Kinase Is Expressed in Brain Neurons

Omri, Boubaker; Crisanti, Patricia; Marty, Marie-Chantal; Alliot, F.; Fagard, Rémy; Molina, Thierry Jo; Pessac, Bernard

doi:10.1046/j.1471-4159.1996.67041360.x

Cited by 48 publications

(47 citation statements)

References 11 publications

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“…Consistent with this hypothesis, our evidence suggests that the Src family tyrosine kinase Lck, which is largely restricted to lymphocytes and some neurons (34,36,37,50), is required for the modification of VP11/12 in Jurkat T cells. Thus, tyrosine phosphorylation of VP11/12 was severely suppressed by the Src family kinase inhibitor PP2 and in the Lck-deficient Jurkat derivative JCaM 1.6.…”

Section: Discussionsupporting

confidence: 83%

“…As one approach to examining this possibility, we asked if the Src family kinase Lck (lymphocyte-specific protein tyrosine kinase) plays any role. Lck is expressed in a tissue-specific fashion, being largely restricted to lymphocytes and neurons (34,36,37,50). In T cells, Lck plays a key role in signaling through the TCR, where it phosphorylates the CD3 and TCR chains of the TCR complex in response to TCR ligation (reviewed in reference 36).…”

Section: Vol 82 2008 Tyrosine Phosphorylation Of Hsv Vp11/12 6103mentioning

confidence: 99%

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Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46

Zahariadis

Wagner²,

Doepker³

et al. 2008

J Virol

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Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play key roles in limiting herpesvirus infections; consequently, many herpesviruses, including herpes simplex virus (HSV), have evolved diverse strategies to evade and/or disarm these killer lymphocytes. Previous studies have shown that CTL and NK cells are functionally inactivated following contact with HSV-infected fibroblasts. During studies of the mechanisms involved, we discovered that HSV-inactivated NK-92 NK cells and Jurkat T cells contain a strikingly prominent, novel, ca. 90-kDa tyrosine-phosphorylated protein that we identified as the HSV tegument protein VP11/12. Inasmuch as VP11/12 produced in fibroblasts and epithelial cells is not obviously tyrosine phosphorylated, these data suggested that VP11/12 serves as the substrate of a cell-type-specific protein tyrosine kinase. Consistent with this hypothesis, VP11/12 was also tyrosine phosphorylated in B lymphocytes, and this modification was severely reduced in Jurkat T cells lacking the lymphocyte-specific Src family kinase Lck. These findings demonstrate that HSV tegument proteins can be differentially modified depending on the cell type infected. Our data also raise the possibility that VP11/12 may modulate one or more lymphocyte-specific signaling pathways or serve another lymphocyte-specific function. However, HSV type 1 mutants lacking the UL46 gene retained the ability to block signaling through the T-cell receptor in Jurkat cells and remained competent to functionally inactivate the NK-92 NK cell line, indicating that VP11/12 is not essential for lymphocyte inactivation. Further studies are therefore required to determine the biological function of tyrosine-phosphorylated VP11/12.

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Section: Discussionsupporting

confidence: 83%

Section: Vol 82 2008 Tyrosine Phosphorylation Of Hsv Vp11/12 6103mentioning

confidence: 99%

Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46

Zahariadis

Wagner²,

Doepker³

et al. 2008

J Virol

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“…Although Lck was consistently and readily detectable in our positive controls, we did not detect it in any of the tissue samples, suggesting that there is a significantly lower level of Lck protein in the normal brain and in grade III and IV tumors compared with Lyn, Fyn, and c-Src proteins. Lck message has been reported to be expressed in the adult mouse brain, but it was noted that its detection by Northern blotting and in situ hybridization required a very long exposure (37) and the intensity of the Lck protein signal in mouse brain lysate, detected by immunoblotting of an unspecified amount of lysate with anti-Lck antisera, was reported to be %10-fold lower than that found in the thymus (37). Thus, although we could not detect Lck protein in our tissue samples, we cannot entirely rule out the possibility that Lck is expressed at very low levels in these samples.…”

Section: Discussionmentioning

confidence: 99%

Lyn Kinase Activity Is the Predominant Cellular Src Kinase Activity in Glioblastoma Tumor Cells

Stettner¹,

Wang²,

Nabors

et al. 2005

Cancer Research

102

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Cellular Src activity modulates cell migration, proliferation, and differentiation, and recent reports suggest that individual members of the Src family may play specific roles in these processes. As we have found that Lyn, but not Fyn, activity promotes migration of glioblastoma cells in response to the cooperative signal generated by platelet-derived growth factor receptor B and integrin A v B 3 , we compared the activity and expression of Lyn and Fyn in glioblastoma (grade IV) tumor biopsy samples with that in anaplastic astrocytoma (grade III) tumors, nonneoplastic brain, and normal autopsy brain samples. Lyn kinase activity was significantly elevated in glioblastoma tumor samples. Notably, the Lyn kinase activity accounted for >90% of pan-Src kinase activity in glioblastoma samples but only %30% of pan-Src kinase activity in the other groups. The levels of phosphorylation of the autophosphorylation site were consistent with significantly higher Lyn activity in glioblastoma tumor tissue than nonneoplastic brain. Although the normalized levels of Lyn protein and the relative levels of Lyn message were significantly higher in glioblastoma samples than nonneoplastic brain, the normalized levels of Lyn protein did not correlate with Lyn activity in the glioblastoma samples. There was no significant difference in the normalized levels of c-Src and Fyn protein and message in the glioblastoma and nonneoplastic brain. Immunostaining revealed that Lyn is located primarily in the glioblastoma cells in the tumor biopsies. These data indicate that Lyn kinase activity is significantly elevated in glioblastoma tumors and suggest that it is the Lyn activity that promotes the malignant phenotype in these tumors. (Cancer Res 2005; 65(13): 5535-43)

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“…Although Lck conventionally is considered a lymphocyte-specific kinase, immunocytochemistry has been used to suggest that Lck also is present in mouse and rat neurons (35,56). However, the neural expression of Lck has not been widely confirmed in the literature, and the reported expression level in the mouse is 10-fold lower in brain than in the thymus (35); moreover, one report indicates that Lck cannot be detected in normal human brain (53).…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes

Wagner

Smiley

2009

J Virol

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The Lck Tyrosine Kinase Is Expressed in Brain Neurons

Cited by 48 publications

References 11 publications

Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46

Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46

Lyn Kinase Activity Is the Predominant Cellular Src Kinase Activity in Glioblastoma Tumor Cells

Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes

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