Preferred Label : BCR Signaling Pathway;
Alternative definition : BIOCARTA: Significant progress has been made towards delineation of the intrinsic
molecular processes that regulate B lymphocyte immune function. Recent observations
have provided a clearer picture of the interactive signaling pathways that emanate
from the mature B cell antigen receptor (BCR) complex and the different precursor
complexes that are expressed during development. Studies have also revealed that the
net functional response to a given antigenic challenge is affected by the combined
action of BCR-dependent signaling pathways, as well as those originating from various
coreceptors expressed by B cells (e.g. CD19, CD22, FcgRIIb and PIR-B).It is now well
established that reversible tyrosine phosphorylation plays an important role in regulating
B cell biology. In particular, binding of antigen to the BCR promotes the activation
of several protein tyrosine kinases (PTK) that, in conjunction with protein tyrosine
phosphatases (PTP), alter the homeostasis of reversible tyrosine phosphorylation in
the resting B cell. The net effect is a transient increase in protein tyrosine phosphorylation
that facilitates the phosphotyrosine dependent formation of effector protein complexes,
promotes targeting of effector proteins to specific microenvironments within the B
cell and initiates the catalytic activation of downstream effector proteins. Studies
have demonstrated that Src family PTKs are activated initially and serve to phosphorylate
CD79a and CD79b thereby creating phosphotyrosine motifs that recruit downstream signaling
proteins. In particular, phosphorylation of the BCR complex leads to the recruitment
and activation of the PTK Syk, which in turn promotes phosphorylation of PLCg, Shc
and Vav. Additionally, the Tec family member Btk is recruited to the plasma membrane
where it is involved in activation of PLCg. Initiation of B lymphocyte activation
is dependent on the tyrosine phosphorylation-dependent formation of multi-molecular
effector protein complexes that activate downstream signaling pathways. The formation
of such complexes was initially hypothesized to occur primarily via effector protein
binding to the BCR complex itself. However, recent studies have demonstrated that
productive signaling via the BCR is in fact dependent on tyrosine phosphorylation
of one or more adapter proteins that play a crucial role in recruitment and organization
of effector proteins at the plasma membrane. The SLP-65/BLNK adapter protein has recently
been shown to play a crucial role in recruitment and activation of key signal transducing
effector proteins in the B cell. After the BCR has been engaged by antigen and the
activation response has been initiated, numerous second messengers and intermediate
signal transducing proteins are activated. These include the production of lipid second
messengers by phosphatidylinositol 3-kinase, and the PLC-dependent hydrolysis of phosphatidylinositol
4,5-bisphosphate to yield diacylglycerol and 1,4,5-inositoltrisphosphate (IP3). DAG
is important for activation of PKC whereas IP3 promote release of calcium from the
endoplasmic reticulum and the subsequent influx Ca2 from the extracellular space.
Numerous intermediate signaling proteins are also activated including the Ras and
Rap1, which are small molecular weight GTPases and these ultimately lead to the activation
of MAP kinases including Erk, JNK and p38. The net effect of second messenger production
and activation of intermediate signaling proteins is the concerted regulation of several
transcription factors that mediate gene transcription in the B cell. (This definition
may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_bcrPathway;
Origin ID : C39005;
UMLS CUI : C1325924;
Semantic type(s)
- UMLS correspondences (same concept)
- has_gene_product_element
- pathway_has_gene_element
