Src, the proto-oncogene tyrosine-protein kinase, is a key protein-tyrosine kinase. It participates in cell growth, division, migration, and survival signaling pathways. From N-to C-terminus, it contains a unique domain, SH3, SH2, a protein-tyrosine kinase domain, and a regulatory tail. It activates downstream signaling pathways like PI3K-AKT, Ras-MAPK, JAK-STAT3, and FAK/Paxillin, crucial for multiple cellular processes [1,2].

Src-knockout mice have provided significant insights. In bone, Src-knockout mice exhibit osteopetrosis as Src is essential for osteoclast-mediated bone resorption and suppresses osteoblast-mediated bone formation [3]. In platelets, studies using SRC knockout mice showed that SRC mediates platelet spreading on fibrinogen, while an activating pathological SRC missense variant in humans affects platelet activation and spreading [4].

In conclusion, Src is vital for numerous biological functions including those in cell growth, bone homeostasis, and platelet function. Gene-knockout mouse models, such as Src-knockout mice, have been instrumental in revealing Src's role in bone-related diseases like osteoporosis and in understanding platelet-related disorders, providing a foundation for potential therapeutic strategies targeting Src in these disease areas.

References:

1. Roskoski, Robert. 2015. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. In Pharmacological research, 94, 9-25. doi:10.1016/j.phrs.2015.01.003. https://pubmed.ncbi.nlm.nih.gov/25662515/

2. Raji, Lukmon, Tetteh, Angelina, Amin, A R M Ruhul. 2023. Role of c-Src in Carcinogenesis and Drug Resistance. In Cancers, 16, . doi:10.3390/cancers16010032. https://pubmed.ncbi.nlm.nih.gov/38201459/

3. Matsubara, Takuma, Yasuda, Kazuma, Mizuta, Kana, Kawaue, Hiroka, Kokabu, Shoichiro. 2022. Tyrosine Kinase Src Is a Regulatory Factor of Bone Homeostasis. In International journal of molecular sciences, 23, . doi:10.3390/ijms23105508. https://pubmed.ncbi.nlm.nih.gov/35628319/

4. De Kock, Lore, Freson, Kathleen. 2020. The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes. In Medicina (Kaunas, Lithuania), 56, . doi:10.3390/medicina56120633. https://pubmed.ncbi.nlm.nih.gov/33255186/