生命科学科研大百科

Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are pro-inflammatory cytokines (1). IL-1α is produced by many cell types, including epithelial cells, monocytes, and macrophages (1,2). It is typically sequestered but can be released during necroptosis or inflammasome activation (3-5). IL-1α is active in both its uncleaved (pro-IL-1α) and cleaved forms and thus acts as an alarmin, initiating signaling through IL-1R1 (6). IL-1β is not active until it is cleaved (7,8). IL-1β expression is induced by inflammatory stimuli, including TLR ligands, IL-1β itself, and tumor necrosis factor-alpha (TNF-α) (1,9,10). IL-1β is primarily synthesized by activated monocytes and macrophages. It activates innate immune cells and polarizes CD4+ T cells toward T helper (Th) 1 and Th17 cells (10).

Exosomes are small (30-150 nm) membrane-bound vesicles that are secreted by various cell types under normal and pathological conditions (1,2). They originate from intracellular multivesicular endosomes upon fusion with the plasma membrane. Exosomes have emerged as an important mechanism of intercellular communication facilitating the transfer of membrane and cytosolic proteins, lipids, and RNA.

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε and δ. Engagement of the TCR complex with antigens presented in Major Histocompatibility Complexes (MHC) induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins.

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε, and δ. Engagement of the TCR complex with antigens presented in major histocompatibility complexes induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins. CD3 phosphorylation is required for downstream signaling through ZAP-70 and p85 subunit of PI-3 kinase, leading to T cell activation, proliferation, and effector functions (1).

Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

MAPK Family; MAPKKK; MAPKK

Lysine Methyltransferase SET domain-containing proteins are potential histone methyltransferases (HMTases), which are classified into subgroups by their putative substrate specificities.

Jak (Janus Kinase) and Stat (signal transducer and activator of transcription) proteins are utilized by receptors for a wide varity of ligands including cytokines, hormones, growth factors, and neurotransmitters. Jaks and Stats play important roles in oncogenesis, tumor progression, angiogenesis, cell motility, immune responses, and stem cell differentiation. Therefore, regulation of Jak/Stat signaling is crucial to prevent aberrant signaling which can lead to disease progression.

The four JAK family members, Jak1, Jak2, Jak3 and Tyk2, range in size from 120 to 140 kDa, and except for Jak3 (leukocyte-JAK), are expressed in most tissues (reviewed in).

Interferon regulatory factors (IRFs) comprise a family of transcription factors that function within the Jak/Stat pathway to regulate interferon (IFN) and IFN-inducible gene expression in response to viral infection.