What is GAS6 Protein

      The GAS6 protein, a member of the vitamin K-dependent family, has emerged as a pivotal player in cellular processes, with a complex structure and multifunctional roles.

      What is GAS6 Protein?

      GAS6, an acronym for Growth Arrest-Specific 6, is a secreted protein encoded by the GAS6 gene located on chromosome 13. Structurally, GAS6 comprises an N-terminal γ-carboxyglutamic acid (Gla) domain, four epidermal growth factor (EGF)-like domains, and a C-terminal sex hormone-binding globulin (SHBG)-like domain. The Gla domain facilitates calcium-dependent interactions with phospholipid membranes, enabling GAS6 to associate with cell surfaces.

      The Structure of GAS6 Protein

      The intricate structure of GAS6 is a testament to its diverse functionalities. The N-terminal Gla domain, essential for membrane interactions, precedes the four EGF-like domains, which contribute to the protein's overall stability and function. The C-terminal SHBG-like domain further enhances the structural complexity of GAS6, emphasizing its role in intricate cellular processes.

      The Function of GAS6 Protein

      GAS6 orchestrates a range of physiological processes through its interaction with TAM receptors (Tyro3, Axl, and Mer). This interaction initiates downstream signaling cascades crucial for cellular functions:

      • Cell Survival and Proliferation

      By activating TAM receptors, GAS6 promotes cell survival and proliferation. This function is particularly vital in tissues characterized by high cell turnover, such as the immune system and reproductive organs.

      • Immune Regulation

      GAS6 exhibits immunomodulatory effects, influencing the activity of immune cells. It regulates the function of macrophages, dendritic cells, and natural killer cells, contributing to immune homeostasis.

      • Phagocytosis

      GAS6 facilitates the clearance of apoptotic cells by enhancing the phagocytic activity of macrophages. This function is critical for maintaining tissue integrity and preventing inflammation.

      GAS6-Related Diseases

      Dysregulation of GAS6 expression or signaling pathways is implicated in various pathological conditions, including cancer, autoimmune disorders, and neurological diseases:

      • Cancer

      Elevated GAS6 expression and TAM receptor activity are observed in numerous cancers. The GAS6/TAM axis promotes tumor cell survival, migration, and invasion, contributing to cancer progression.

      • Autoimmune Disorders

      Aberrant GAS6 signaling is linked to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, where it may modulate immune responses and contribute to tissue damage.

      • Neurological Disorders

      The GAS6/TAM system plays a role in neuroinflammation and neurodegenerative diseases. It influences microglial activation and phagocytosis in the central nervous system, impacting the progression of conditions like Alzheimer's disease.

      GAS6 Related Signaling Pathways

      The intricate signaling pathways activated by GAS6 involve complex molecular interactions, influencing various cellular responses:

      • PI3K-Akt Pathway

      Activation of the PI3K-Akt pathway is a common downstream effect of GAS6 binding to TAM receptors, promoting cell survival, growth, and metabolism.

      • MAPK/ERK Pathway

      GAS6 activates the MAPK/ERK pathway, contributing to cell proliferation and differentiation, crucial for maintaining tissue homeostasis.

      • NF-κB Pathway

      GAS6 can activate the NF-κB pathway, influencing immune responses and inflammation, offering insights into its role in various diseases.

      Schematic representation of GAS6/TAM signaling pathway. (Law, L.A., et al. 2018)

      Figure 1. Schematic representation of GAS6/TAM signaling pathway. (Law, L.A., et al. 2018)

      Applications of GAS6 in Biomedical Research

      The unique properties of GAS6 make it a promising candidate for diverse biomedical applications:

      • Cancer Therapy

      Targeting the GAS6/TAM axis in cancer cells is a burgeoning area of research. Inhibitors of TAM receptors or GAS6 blocking antibodies hold potential to impede tumor growth and metastasis.

      • Neurodegenerative Diseases

      Modulating GAS6 signaling is being explored for therapeutic interventions in neurodegenerative diseases. Insights into its role in neuroinflammation may pave the way for novel treatments for conditions like Alzheimer's and Parkinson's.

      • Immunotherapy

      The immunomodulatory effects of GAS6 present opportunities for developing novel immunotherapies. Harnessing its potential could revolutionize the treatment of autoimmune diseases.

      • Regenerative Medicine

      GAS6's role in cell survival and proliferation positions it as a promising candidate for regenerative medicine. Manipulating GAS6 signaling may enhance tissue repair and regeneration, opening avenues for innovative therapeutic strategies.

      GAS6 protein, with its intricate structure and diverse functions, has become a focal point in molecular biology research. From its roles in cell survival and immune regulation to its implications in diseases and potential applications in biomedical fields, GAS6 continues to unveil its wonders, offering new avenues for understanding and manipulating cellular processes for therapeutic purposes.

      Recommended Products for GAS6 Protein

      Cat.# Species Product name Source (Host) Tag
      GAS6-613H Human Active Recombinant Human Growth Arrest-Specific 6, His-tagged Mammalian cells His
      GAS6-288TH Human Recombinant Human GAS6 full-length, GST-tagged Wheat Germ GST
      GAS6-3014H Human Recombinant Human GAS6 Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
      GAS6-382H Human Recombinant Human GAS6(Ala31-Ala678) Protein, C-Fc-tagged HEK293 Fc
      GAS6-2540H Human Recombinant Human GAS6 Protein (Trp379-Ala678), N-His tagged E.coli N-His
      Gas6-483M Mouse Active Recombinant Mouse Gas6, His-tagged Mammalian cells His
      Gas6-196M Mouse Recombinant Mouse Gas6 Protein, His/GST-tagged E.coli His/GST
      Gas6-197R Rat Recombinant Rat Gas6 Protein, His-tagged E.coli His
      Gas6-1563R Rat Recombinant Rat Gas6 Protein, His&GST-tagged E.coli N-His&GST
      GAS6-10341Z Zebrafish Recombinant Zebrafish GAS6 Mammalian Cell His

      Reference

      • Law, L.A., et al. GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis. Front Med (Lausanne). 2018, 5: 137.