Diagram illustrating the PS–Tyro3–Akt cell survival signaling pathways

A diagram illustrating the PS–Tyro3–Akt cell survival signaling pathways. Activation of the PS–Tyro3–PI3K–Akt axis (blue) phosphorylates Mdm2 and Bad, the Akt substrates. pMdm2 lowers p53, a key upstream initiator of apoptosis in neurons, which downregulates Bax, the proapoptotic Bcl-2 family member and a transcriptional product of p53. Bad (Bcl2/Bcl-XL antagonist), a proapoptotic member of the Bcl-2 family, is inactivated by Akt-mediated phosphorylation. PS-induced changes in Bax, Bcl-2, and Bcl-XL stabilize the mitochondrial membranes, prevent drop in ATP and mitochondrial membrane potential, and inhibit caspase-9 activation. In addition to the presently demonstrated PS-mediated inhibition of caspase-dependent nuclear translocation of AIF, activated Akt can also protect against caspase-independent cell death and/or block AIF translocation in a caspase-independent manner, as reported by others (; ; ).

Publication

Protein S Protects Neurons from Excitotoxic Injury by Activating the TAM Receptor Tyro3–Phosphatidylinositol 3-Kinase–Akt Pathway through Its Sex Hormone-Binding Globulin-Like Region. (2010) Zhihui Zhong, et al. J Neurosci. 2010 Nov 17;30(46):15521-15534. Figure: F7. All organisms Mus musculus Rattus norvegicus Bos taurus Equus asinus Homo sapiens Ovis aries Capra hircus Oryctolagus cuniculus Drosophila melanogaster

Disease mentions