Question

Following antigenic stimulation, phosphorylation of _________ relieves inhibition of the transcription factor

Answer 1

Answer: zap70, ITAM.

Explanation:

An antigen is any substance that is capable of stimulating an immune response by activating lymphocytes, which are the body’s infection-fighting white blood cells. Examples of antigens could be proteins that are part of bacteria or viruses or components of serum and red blood cells from other individuals, all of them are foreign antigens originated outside the body. However, there can also be autoantigens (which are self-antigens), originated within the body. In normal conditions, the body is able to distinguish self from nonself. And the antigens that represent a danger induces an immune response by stimulating the lymphocytes to produce antibody or to attack the antigen directly. This is called an antigenic stimulation of the immune system.

ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein that is part of the T cell receptor, thereby it plays a critical role in T-cell signaling. When the TCR (receptor of T cells) is activated by the presentation of the specific antigen through the MHC, a protein called Lck acts to phosphorylate the intracellular CD3 chains and the ζ chains of the TCR complex, allowing the binding of the cytoplasmic tyrosine kinase, ZAP-70. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates another molecule in the signaling cascade called LAT (short for Linker of Activated T cells), a transmembrane protein that serves as an anchor site for several other proteins. The tyrosine phosphorylation cascade initiated by the Lck culminates in the intracellular mobilization of calcium ion (Ca2+) and the activation of important signaling cascades within the lymphocytes. These include the Ras-MEK-ERK pathway, which is based on activating certain transcription factors such as NFAT, NFκB and AP-1. These transcription factors regulate the production of of certain gene products, most notably cytokines such as interleukin-2 that promote the long-term proliferation and differentiation of activated lymphocytes.

The ITAM motifs (immunoreceptor tyrosine-based activation motif) are sequences of four amino acids present in the intracellular tails of certain proteins that serve as receptors within the immune system. Thus, some receptors such as the TCR have ITAM sequences that, when activated, trigger an intracellular reaction based on consecutive phosphorylations.  Kinases are recruited for this purpose.

So, ZAP-70 is a protein tyrosine kinase with a role in T-cell receptor signal transduction. During T-cell activation, ZAP-70 binds to ITAM and becomes tyrosine phosphorylated. The binding of ZAP-70 to the phosphorylated ITAM is able to activate its kinase activity, and relieves the inhibition of the transcription factor which regulates genes that are involved in the immune reaction.