Prolactin and the Secretion of Insulin and Glucagon by the Pancreas

Foà, Piero P.; Galansino, Giorgio; Costa, Eduardo

doi:10.1152/ajplegacy.1955.182.3.493

Cited by 8 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As discussed in the introduction, JAK2 is the essential signal transducer linking growth hormone and prolactin receptor stimulation to STAT5 phosphorylation, and this signaling network is essential for the development and preservation of functional pancreatic β-islet cell mass [32-37]. The progressive loss of functional pancreatic β-islet mass is the hallmark event in the pathogenesis of type II diabetes mellitus, and chronic oxidative stress contributes to its demise [38].…”

Section: Resultsmentioning

confidence: 99%

“…Growth hormone (GH) and prolactin, two hormones essential for normal development of pancreatic islet function and insulin secretion [32,33], require JAK2 as an essential signal transducer to activate STAT5 in the pancreas [34]. Transgenic animal models demonstrate the need for functional prolactin receptors [35], growth hormone receptors [36], and STAT5 [37] in preserving functional pancreatic β-islet cell mass.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of a redox-sensitive switch within the JAK2 catalytic domain

Smith

Patil

Patlolla

et al. 2012

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Four cysteine residues (Cys866, Cys917, Cysl094, and Cys1105) have direct roles in cooperatively regulating Janus kinase 2 (JAK2) catalytic activity. Additional site-directed mutagenesis experiments now provide evidence that two of these residues (Cys866 and Cys917) act together as a redox-sensitive switch, allowing JAK2's catalytic activity to be directly regulated by the redox state of the cell. We created several variants of the truncated JAK2 (GST/(NΔ661)rJAK2), which incorporated cysteine-to-serine or cysteine-to-alanine mutations. The catalytic activities of these mutant enzymes were evaluated by in vitro autokinase assays and by in situ autophosphorylation and transphosphorylation assays. Cysteine-to-alanine mutagenesis revealed that the mechanistic role of Cys866 and Cys917 is functionally distinct from that of Cysl094 and Cys1105. Most notable is the observation that the robust activity of the CC866.917AA mutant is unaltered by pretreatment with dithiothreitol or o-iodosobenzoate, unlike all other JAK2 variants previously examined. This work provides the first direct evidence for a cysteine-based redox-sensitive switch that regulates JAK2 catalytic activity. The presence of this redox-sensitive switch predicts that reactive oxygen species can impair the cell's response to JAK-coupled cytokines under conditions of oxidative stress, which we confirm in a murine pancreatic β-islet cell line.

show abstract

Section: Resultsmentioning

confidence: 99%