Page 31 - M. Immunology

TAM Family of Receptor Tyrosine Kinases: roles in anti-inflammation
through regulating Macrophage Function
In-Byung Park and Taehoon Chun
Department of Biotechnology, Major in Molecular Bioengineering,
Korea University Graduate School, Seoul, Republic of Korea

BACKGROUND AIM
⚫ Macrophage is a key mediator of innate immunity which controls initial inflammation and immune homeostasis (Mosser and ⚫ We will focus on
Edwards, 2008). Macrophage are classified as m1 or M2 phenotype depending on which stimulus they are first exposed to within a mechanisms how TAM
certain microenvironment (Mills et al., 2000). receptor signaling inhibits
⚫ Receptor tyrosine kinases (RTKs) are essential membrane proteins that transmit extracellular signal through phosphorylation of inflammatory responses via
tyrosine residue within their cytoplasmic domains (Robinson et al., 2000). Among 20 subfamilies of RTKs, TAM receptor family manipulation of macrophage
consisting of Tyro3, Axl, and Mer is the main family that gives a pleiotropic anti-inflammatory response. phenotype.
RESULTS
Fig. 1. Structures of TAM family receptors and their
ligands.
Ig superfamily domains of each TAM receptor recognize their
ligands. The extracellular domain of each TAM family receptor
contains two Ig superfamily domains and two fibronectin type
Ⅲ domains. The cytoplasmic domain of each TAM family
receptor contains a conserved protein tyrosine kinase (PTK)
domain and immunoreceptor tyrosine based inhibitory motif
(ITIM) domain. Autophosphorylation sites of each TAM family
receptor are located within PTK domain. In addition, the
cytoplasmic domain of each TAM family receptor includes
well-conserved “KW(I/L)A(I/L)ES” signature sequence.
Gas6 can bind to all three TAM family receptors with the
highest affinity to Axl, whereas Pros1 can interact with Mer or
Tyro3, but not Axl. Gas6 and Pros1 have γ-carboxyglutamate-
rich domain (Gla domain) at their amino terminus. Additionally,
the proteins contain four epidermal growth factor (EGF)-like
domains and one sex hormone binding globulin (SHBG)
domain which consists of two globular laminin G-like (LG)
domain.

Fig. 2. Pleotropic inhibition of inflammatory responses by TAM family receptors expressed on macrophages.
(A) TAM receptor signaling enhances phagocytosis of apoptotic cells.
(B) Attenuation of type I IFN-mediated inflammatory responses by TAM receptor signaling.
(C) TAM receptor signaling suppresses NLRP3 inflammasome activation by autophage induction.
(D) TAM receptor signaling inhibits M1 macrophage polarization and enhances M2 macrophage polarization by induction of IL-10.

CONCLUSION REFERENCES
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ACKNOWLEDGEMENTS CONTACT INFORMATION
⚫ This work was supported by a grant from the Next-Generation BioGreen 21 Program E-mail address: tnquddls@korea.ac.kr
(Project No. PJ01327101), Rural Development Administration, Republic of Korea. Address: Life science West Building, Korea University, Seongbuk-
gu, Anam-ro 145, Seoul