Author response: A Fyn biosensor reveals pulsatile, spatially localized kinase activity and signaling crosstalk in live mammalian cells

Mukherjee, Ananya; Singh, Randhir; Udayan, Sreeram; Biswas, Sayan; Reddy, P. Purushotham; Manmadhan, Saumya; George, Geen; Kumar, Shilpa Dilip; Das, Ranabir; Rao, Balaji M.; Gulyani, Akash

doi:10.7554/elife.50571.sa2

Cited by 1 publication

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“…Src family kinases (SFKs) are non-receptor-type tyrosine kinases and include two subfamilies: Src-and Lyn-related kinases (Truong and Carroll, 2013). Three types of Srcrelated kinases, namely, Src, Fyn, and Yes, are expressed in the developing brain, which play important roles in many signaling pathways and various biological activities, such as gene transcription, cell adhesion, cell cycle progression, immune response, apoptosis, migration, and transformation (Stein et al, 1994;Mukherjee et al, 2020). Based on accumulating evidence, SFKs are important for neuronal outgrowth and myelination on OL (Umemori et al, 1994;Liang et al, 2004;Bauer et al, 2009;Rouer, 2010).…”

Section: Introductionmentioning

confidence: 99%

Src Family Kinases Inhibition Ameliorates Hypoxic-Ischemic Brain Injury in Immature Rats

Qiu

Qian

et al. 2021

Front. Cell. Neurosci.

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Hypoxic-ischemic (HI) injury is one of the initial factors contributing to neonatal brain injury. Src family kinases (SFKs) are considered to act as molecular hubs for N-methyl-d-aspartate receptor (NMDAR) regulation and participate in the HI injury process. The objectives of this study were to evaluate the levels of phospho-Src (p-Src), the relationship between NMDARs and SFKs, and the effects of SFK inhibition on an immature rat HI brain injury model. The model was induced in 3-day-old Sprague–Dawley rats using the Rice-Vannucci model operation. The level of p-Src was evaluated using Western blotting. The association of NMDARs with SFKs was detected using Western blotting and coimmunoprecipitation. After intraperitoneal injection of 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2), an SFK-selective inhibitor, neuropathological changes were observed by performing H&E and immunofluorescence staining, and the neurological functions were assessed using the following behavioral tests: modified neurological severity score, open field test, and Morris water maze test. The levels of p-Src first decreased at 0 h after injury, increased at 2 h after injury, and continuously decreased from 6 h to 3 days. Along with the increased p-Src levels observed at 2 h after injury, the phosphorylation of NMDAR subunit NR2B at tyrosine 1472 was increased. Following the administration of PP2, the increased p-Src and NMDAR-2B levels detected at 2 h after injury were decreased, and tissue injury and myelin basic protein expression were improved at 7 days after injury. The PP2 intervention improved the performance of injured rats on behavioral tests. In conclusion, we determined the patterns of p-Src expression after HI brain injury in immature rats and showed a relationship with the activated NMDA receptor. The inhibition of p-Src ameliorates neuropathological changes and damages neurological functions induced by HI injury.

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