T cell activation and signal transduction

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

Src Kinases

Src family kinases are named after the transforming gene of Rous sarcoma virus, the first animal tumor virus identified.

Src (pronounced "sarc" as it is short for sarcoma) is a family of proto-oncogenic tyrosine kinases discovered by J. Michael Bishop and Harold Varmus, for which they won the 1989 Nobel Prize. The discovery of Src family proteins has been instrumental to the understanding of cancer as a disease where normally healthy cellular signalling has gone awry.

The Src family includes 9 members:

SrcA subfamily
- Src
- Yes
- Fyn
- Fgr

SrcB subfamily
- Lck
- Hck
- Blk
- Lyn

Frk is in its own subfamily

Phosphorylation events in T cell activation:

Lck (Src kinases Lyn, Fyn, Blk in B cells)
ZAP (Syk in B cells)

PLC
LAT (SLP/Btk in B cells)
Grb2

SOS
RAS, MAPK

NAN (NFAT, AP-1, NFkB)

C-src tyrosine kinase

C-src tyrosine kinase, also known as CSK, includes an SH2 domain, an SH3 domain, and a tyrosine kinase domain. C-src also acts on the LYN and FYN kinases.

LYN

LYN is V-yes-1 Yamaguchi sarcoma viral related oncogene homolog. LYN is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells and in neural tissues. LYN is associated with cell surface receptor proteins, including the B cell antigen receptor (BCR), CD40, or CD19.

Lck

Lck (or leukocyte-specific protein tyrosine kinase) is a protein that is found inside lymphocytes. Lck is a member of the Src family of tyrosine kinases.

SYK

SYK (Spleen tyrosine kinase) is an enyzme encoded by the SYK gene. SYK and ZAP-70 are members of the Syk family of tyrosine kinases. Please make a distinction between the Src family of tyrosine kinases (9 members, listed above) and the Syk family of tyrosine kinases (SYK and ZAP-70).

Within B and T cells respectively, SYK and ZAP-70 transmit signals from the B-Cell receptor and T-Cell receptor.

B-cells have SYK
T-cells have ZAP

LAT

LAT (Linker of Activated T cells) is a protein phosphorylated by ZAP70/SYK protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway.

B cell activation and signal transduction (click on the little for full text)

Phosphorylation events in B cell activation:

Src kinases Lyn, Fyn, Blk
Syk

PLC
SLP/Btk
Grb2

SOS
RAS, MAPK

NAN (NFAT, AP-1, NFkB)

Complement receptor CD21 (CR2) activates BCR if the antigen is opsonized by C3b component of the complement.

CR2-CD19-CD81 complex is expressed on the surface of B lymphocytes.

Activation of B cells depends on the following:

- CD 19 and CD21 (CR2)
- TAPA 1
- CD81
- ITAM (universal activation motif)

Inhibition of B cells depends on the following:

- CD22
- CD45
- FcγRIIb (CD32)
- CTLA-4 (Cytotoxic T-lymphocyte antigen-4)
- ITIM (universal inhibition motif)


T and B Cells - Naive and Memory Cell Markers (click to enlarge the image).

T cell activation involves all of the following steps EXCEPT:

A. RAS-MAPK pathway

B. activation of Syk

C. activation of NFAT

D. activation of Protein Kinase C

Answer: B. Syk is part of the B cell activation. ZAP-70 is its equivalent in T cells.

References

Src (gene). Wikipedia.
LYN. Wikipedia.
Lck. Wikipedia.
SYK. Wikipedia.
LAT, Linker of activated T cells. Wikipedia.

Related reading

Discovery of T-cell Receptors (video)

National Jewish Health scientists John Kappler, PhD, and Philippa Marrack, PhD, discuss their discovery of the T-cell receptor - the protein found on the surface of T Cells that helps detect specific antigens, or foreign invaders, in the body:

Redirecting T Cells - NEJM, 2011.
Genomics and the Multifactorial Nature of Human Autoimmune Disease. NEJM, 2011.

Published: 08/29/2009
Updated: 11/29/2012