PTK2B, also known as proline-rich tyrosine kinase 2 (Pyk2), is a non-receptor protein tyrosine kinase. It is involved in multiple biological processes, such as the regulation of antiviral innate immune responses, microglial functions related to Alzheimer's disease (AD), and immune responses in neutrophils relevant to ulcerative colitis (UC). In the antiviral response, it enhances the oligomerization of TBK1 and STING, regulating STING-TBK1 activation [1]. In AD, it may link Aβ and tau pathologies in microglia [2]. In UC, it is involved in neutrophil-mediated mucosal inflammation regulation [3].

Genetic models have been crucial in understanding PTK2B's functions. Ptk2b-deficient mice are more susceptible to viral infection, highlighting its role in antiviral innate immunity [1]. In the context of folliculogenesis, Ptk2b ablation in mice improves female fecundity by promoting folliculogenesis via the Erk pathway [4]. In ulcerative colitis, DSS-induced colitis model in Ptk2B KO mice shows more severe colitis symptoms, indicating PTK2B's protective role in mucosal inflammation by regulating neutrophil migration [3].

In summary, PTK2B plays essential roles in various biological processes and disease conditions. Mouse models, especially KO models, have been instrumental in revealing its functions in antiviral immunity, AD-related neuropathology, and UC-associated mucosal inflammation. These findings provide potential therapeutic targets for diseases related to these processes [1,2,3,4].

References:

1. Lin, Yongfang, Yang, Jing, Yang, Qili, Chen, Dahua, Sun, Qinmiao. 2023. PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling. In Nature communications, 14, 7567. doi:10.1038/s41467-023-43419-4. https://pubmed.ncbi.nlm.nih.gov/37989995/

2. Guo, Yun, Sun, Cheng-Kun, Tang, Lian, Tan, Meng-Shan. . Microglia PTK2B/Pyk2 in the Pathogenesis of Alzheimer's Disease. In Current Alzheimer research, 20, 692-704. doi:10.2174/0115672050299004240129051655. https://pubmed.ncbi.nlm.nih.gov/38321895/

3. Zhou, Guangxi, Zhu, Fengqin, Zhang, Hairong, Dong, Guanjun, Xiong, Huabao. . PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e22967. doi:10.1096/fj.202201995RR. https://pubmed.ncbi.nlm.nih.gov/37269155/

4. Cong, Yanyan, Wu, Haibo, Bian, Xuejiao, Suo, Lun, Kuang, Yanping. 2020. Ptk2b deletion improves mice folliculogenesis and fecundity via inhibiting follicle loss mediated by Erk pathway. In Journal of cellular physiology, 236, 1043-1053. doi:10.1002/jcp.29914. https://pubmed.ncbi.nlm.nih.gov/32608523/