Src kinase-associated phosphoprotein 1 is an
adapter protein that in humans is encoded by the ''SKAP1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
This gene encodes a
T cell
T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
adapter protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a
PH domain
Pleckstrin homology domain (PH domain) or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.
This domain can bind phosph ...
and C-terminal
SH3 domain
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of ph ...
. Along with the adhesion and degranulation-promoting adapter protein, the encoded protein plays a critical role in
inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of
integrin
Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s.
The demonstration that SKAP1 regulates
LFA-1 adhesion was made by retroviral infection and by the SKAP1 deficient mouse. Additional work has implicated SKAP1 in binding to the
exchange factor RasGRP1
RAS guanyl-releasing protein 1 is a protein that in humans is encoded by the ''RASGRP1'' gene.
Function
RAS guanyl nucleotide-releasing protein (RASGRP) is a member of a family of genes characterized by the presence of a Ras superfamily guan ...
and in regulating
ERK activation in T-cells.
[Schneider H., Wang H., Raab M., Valk E., Smith X., Lovatt M., Wu Z., Strebhardt K, Rudd, CE. Adaptor SKAP55 binds RasGRP1 and negatively regulates p21ras and the ERK pathway in T-cells. (2008) PLoS ONE. 3, 1718.]
Interactions
SKAP1 has been shown to
interact with
FYN
Proto-oncogene tyrosine-protein kinase Fyn (p59-FYN, Slk, Syn, MGC45350, Gene ID 2534) is an enzyme that in humans is encoded by the ''FYN'' gene.
Fyn is a 59-kDa member of the Src family of kinases typically associated with T-cell and neurona ...
,
PTPRC
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocy ...
and
FYB.
References
Further reading
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