Src is the best understood member of a family of 9 tyrosine kinases that regulates cellular responses to extracellular stimuli. The Src family of non-receptor tyrosine kinases are integrators of divergent signal transduction pathways which regulate numerous cellular processes, including tumorigenicity and angiogenesis[3]. Dysfunction of Src, through overexpression or increased activation, has profound effects on basic cellular functions. Elevated Src expression and/or activation is evident across a wide range of solid tumour types.[4]. PP1 is a potent, and Src family-selective tyrosine kinase inhibitor with IC50 of 5 and 6 nM for Lck and Fyn, respectively. PP1 inhibits Lck (IC50=5 nM) and FynT (IC50=6 nM) in vitro at concentrations significantly lower than those required to inhibit ZAP-70 (IC50>100 μM), JAK2 (IC50>50 μM), the EGFR kinase, and protein kinase A. PP1 inhibits whole cell tyrosine phosphorylation and proliferation in T cells stimulated with anti-CD3 and mitogens. PP1 selectively inhibits IL-2 gene expression over GM-CSF and IL-2R gene induction in human T cells[5]. PP1 also blocks TGF-β-mediated cellular responses by directly inhibiting type I TGF-β receptors (IC50 = 50 nM) in a manner unrelated to Src signaling[6].
PP1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
NRK-49F cells
1 µM, 2 µM, 5 µM
24 hours
PP1 dose-dependently inhibited TGF-β1-induced expression of α-SMA, fibronectin, and collagen I, with maximum inhibition at 5 μM.
Kidney Int. 2016 Jan;89(1):68-81.
HUES8, HUES49, H9, iPSC 11b hPSCs
25 µM
24 hours
PP1 treatment significantly improved the differentiation capacity of multiple hPSC lines, increasing the percentage and total number of Brachy+ cells.
J Cell Biol. 2015 Sep 28;210(7):1257-68.
HUES6 hPSCs
25-50 µM
24 hours
PP1 treatment significantly improved the differentiation capacity of HUES6 hPSCs, increasing the percentage and total number of Brachy+ cells in a dose-dependent manner.
J Cell Biol. 2015 Sep 28;210(7):1257-68.
H460 non-small cell lung cancer cells
5 µM
48 hours
PP1 inhibited the proliferation, migration, and invasion of H460 cells and reversed the morphine-induced antiapoptotic effect
Cancer Cell Int. 2021 Nov 25;21(1):622.
PP1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Unilateral ureteral obstruction (UUO) model
Intraperitoneal injection
2 mg/kg
Once daily for 7 or 14 days
PP1 significantly reduced ECM deposition in fibrotic kidneys, inhibited the expression of fibronectin, α-SMA, and collagen I, and attenuated renal interstitial fibrosis.
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