signal transduction-lecture 15

What is the antigen receptor on B cells?

BCR (surface IgM/IgD) with Igα/Igβ heterodimer containing ITAMs

What is the antigen receptor on T cells?

TCR αβ heterodimer with CD3 complex (γ, δ, ε) and ζ chains containing ITAMs

Define tyrosine kinases.

Enzymes that phosphorylate tyrosine residues on ITAMs to initiate downstream signaling (e.g., Lck, Fyn, Lyn, ZAP-70, Syk)

Define ITAMs.

Immunoreceptor Tyrosine-based Activation Motifs; phosphorylated to recruit kinases/adaptors for signaling

Define scaffolding/adaptor molecules.

Proteins that organize signaling complexes and link receptors to downstream enzymes (e.g., LAT, BLNK, SLP-76)

Define PLC-γ.

Phospholipase C-γ; cleaves PIP2 into DAG and IP3 after receptor activation

Define calcineurin.

Ca²⁺-calmodulin–dependent phosphatase that activates NFAT transcription factor

Define small G-proteins.

Molecular switches (Ras, Rac, Rho) controlling MAPK signaling and cytoskeleton changes

Define transcription factors in lymphocyte signaling.

NFAT, NF-κB, AP-1; drive cytokine production and survival genes

Define TCR costimulation.

Secondary signaling via CD28 binding B7 (CD80/86), required for full T cell activation

What kinase is recruited by BCR ITAMs?

Syk

What kinase is recruited by TCR ITAMs?

ZAP-70

What co-receptor enhances BCR signaling?

CD19/CD21 complex

What co-receptor enhances TCR signaling?

CD4 or CD8 binding MHC and stabilizing TCR–MHC interaction

List receptors that use ITAMs.

TCR, BCR, FcεRI, FcγR, NK activating receptors

List receptors that use ITIMs.

FcγRIIB, NK inhibitory receptors (KIRs, NKG2A), PD-1

What is the outcome of ITAM signaling?

Cell activation, proliferation, survival, cytokine secretion

What is the outcome of ITIM signaling?

Signal inhibition via phosphatases (SHP-1, SHP-2)

Compare BCR vs TCR main kinases.

BCR uses Lyn and Syk; TCR uses Lck and ZAP-70

Compare BCR vs TCR adaptors.

BCR uses BLNK; TCR uses LAT and SLP-76

Compare BCR vs TCR costimulation.

B cells: CD19/CD21; T cells: CD28-B7

Compare main function of BCR vs TCR.

BCR recognizes intact antigen; TCR recognizes peptide-MHC

What is the role of ITAMs?

Contain tyrosines phosphorylated by Src kinases, recruit ZAP-70 (TCR) or Syk (BCR) to initiate signaling

What is the role of ITIMs?

Inhibitory motifs that recruit SHP-1/2 phosphatases to down-regulate activation

What is the role of Lck in TCR signaling?

Phosphorylates ITAMs on CD3/ζ chains, enabling ZAP-70 binding

What is the role of Lyn in BCR signaling?

Phosphorylates ITAMs on Igα/Igβ, enabling Syk binding

What is the role of ZAP-70?

Binds phosphorylated ITAMs in TCR signaling and phosphorylates LAT and SLP-76

What is the role of Syk?

Binds phosphorylated ITAMs in BCR signaling and phosphorylates BLNK

What is the role of LAT and SLP-76?

Adaptor proteins in TCR signaling that recruit PLC-γ1, Grb2, and others

What is the role of BLNK?

Adaptor protein in BCR signaling that links Syk to PLC-γ2 and Btk

What is the role of PLC-γ1/2?

Hydrolyze PIP2 into DAG and IP3, producing second messengers

What is the role of IP3?

Triggers Ca²⁺ release from ER stores, increasing cytosolic calcium

What is the role of DAG?

Activates PKC-θ and RasGRP, leading to NFκB and AP-1 activation

What is the role of calcineurin?

Ca²⁺/calmodulin-dependent phosphatase that dephosphorylates NFAT

What is the role of calmodulin?

Binds Ca²⁺ and activates calcineurin

What is the role of Ras?

Small GTPase molecular switch that activates Raf → MAPK → AP-1

What is the role of RasGRP?

GEF that activates Ras by facilitating GDP to GTP exchange

What is the role of IKK?

Phosphorylates IκB, causing its degradation and freeing NFκB

What is the role of NFAT?

Transcription factor dephosphorylated by calcineurin that enters the nucleus to promote IL-2 transcription

What is the role of NFκB?

Transcription factor released after IκB degradation that promotes survival and cytokine production

What is the role of AP-1?

Transcription factor (Fos/Jun) activated by MAPK signaling

What is the role of CD28?

T cell costimulatory receptor that binds B7 (CD80/86) to enhance IL-2 transcription and survival

What is the role of CD19/CD21?

B cell coreceptor complex that amplifies BCR signaling strength

What is the role of CD4/CD8?

TCR co-receptors that bind MHC II/I and stabilize TCR-MHC interactions, bringing Lck close to ITAMs

What is the role of CD45?

Tyrosine phosphatase that dephosphorylates and activates Lck

What transcription factors are activated downstream of antigen receptor signaling?

NFAT, NFκB, and AP-1

What is signal transduction?

Conversion of extracellular signals into intracellular processes affecting gene expression and function