Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity

Gay, Denise; Ramón, Hilda E.; Oliver, Peter

doi:10.1007/s12026-008-8034-0

Cited by 24 publications

(16 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Engagement of the T cell receptor (TCR) with its cognate peptide/MHC initiates a cascade of signaling events resulting in T-cell activation. Limiting the extent and duration of TCR signaling ensures a tightly constrained response, protecting cells from the deleterious impact of chronic activation [67]. Unstimulated ampk -/- lymphocytes proliferated more than ampk +/+ lymphocytes, a finding presumably do to unrestricted activation.…”

Section: Discussionmentioning

confidence: 99%

AMPKα1-Sensitivity of Orai1 and Ca<sup>2+</sup> Entry in T - Lymphocytes

Bhavsar

Schmidt²,

Bobbala³

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: T-lymphocyte activation and function critically depends on Ca²⁺ signaling, which is regulated by store operated Ca²⁺ entry (SOCE). Human and mouse T lymphocytes express AMP activated kinase AMPKα1, which is rapidly activated following elevation of cytosolic Ca²⁺ concentration ([Ca²⁺]_i) by treatment of the cells with Ca²⁺ ionophore or following inhibition of endosomal Ca²⁺ ATPase with thapsigargin. AMPK is further activated by triggering of the T cell antigen receptor (TCR). The present study explored whether AMPK influences Ca²⁺ entry and Ca²⁺-sensitive regulation of T-lymphocyte function. Methods: T-lymphocytes were isolated and cultured from AMPKα1-deficient (ampk^-/-) mice and from their wildtype (ampk^+/+) littermates. The phenotype of the cells was analysed by flow cytometry, [Ca²⁺]_i estimated from Fura-2 fluorescence, SOCE from increase of [Ca²⁺]_i following thapsigargin treatment (1 µM), and cell function analysed by measuring cytokine secretion and western blotting. Results: Expression of surface markers in CD4⁺ and CD8⁺ T-cells were similar in ampk^-/- and ampk^+/+ T-lymphocyte blasts. Moreover, total STIM1 protein abundance was similar in ampk^-/- and ampk^+/+ T-lymphocyte blasts. However, Orai1 cell membrane protein abundance was significantly higher in ampk^-/- than in ampk^+/+ T-lymphocyte blasts. SOCE and increase of [Ca²⁺]_i following TCR activation by triggering TCR with anti-CD3 and cross-linking secondary antibody were both significantly more pronounced in ampk^-/- than in ampk^+/+ T-lymphocyte blasts. The difference of Ca²⁺ entry between ampk^-/- and ampk^+/+ T-lymphocytes was abrogated by Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-APB, 50 µM). Proliferation of unstimulated ampk^-/- lymphocytes was higher than proliferation of ampk^+/+ T-lymphocytes, a difference reversed by Orai1 silencing. Conclusions: AMPK downregulates Orai1 and thus SOCE in T-lymphocytes and thus participates in negative feed-back regulation of cytosolic Ca²⁺ activity.

show abstract

Section: Discussionmentioning

confidence: 99%

AMPKα1-Sensitivity of Orai1 and Ca<sup>2+</sup> Entry in T - Lymphocytes

Bhavsar

Schmidt²,

Bobbala³

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Ubiquitination is also important for proper functioning of the Wnt/β-catenin/APC pathway (Voutsadakis 2008), and both Nedd4 and Ube4a are genes regulated by NT3 treatment that are involved in ubiquitination (Caren et al . 2006, Gay et al . 2008).…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

Nilsson¹,

Dole²,

Skinner³

2009

Reproduction

View full text Add to dashboard Cite

Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100–250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrphostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition.

show abstract

“…In addition, APC regulates β-catenin in the Wnt/frizzled/β-catenin signaling pathway, and this signaling pathway has been shown to be important for ovarian and follicular development (Richards et al 2002, Ricken et al 2002. Ubiquitination is also important for proper functioning of the Wnt/β-catenin/APC pathway (Voutsadakis 2008), and both Nedd4 and Ube4a are genes regulated by NT3 treatment that are involved in ubiquitination (Caren et al 2006, Gay et al 2008. Many of these genes, of course, could also function in pathways unrelated to granulosa cell development.…”

Section: Discussionmentioning

confidence: 99%

Neurotrophin Nt3 Promotes Ovarian Primordial to Primary Follicle Transition.

Nilsson

Dole²,

Skinner³

2009

Biology of Reproduction

View full text Add to dashboard Cite

Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100-250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/ neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrphostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition.

show abstract

Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity

Cited by 24 publications

References 79 publications

AMPKα1-Sensitivity of Orai1 and Ca<sup>2+</sup> Entry in T - Lymphocytes

AMPKα1-Sensitivity of Orai1 and Ca<sup>2+</sup> Entry in T - Lymphocytes

Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

Neurotrophin Nt3 Promotes Ovarian Primordial to Primary Follicle Transition.

Contact Info

Product

Resources

About