Src Kinase Associated Phosphoprotein 1 (SKAP1)

SCAP1; SKAP55; pp55; Src Family Associated Phosphoprotein 1; Src kinase-associated phosphoprotein of 55 kDa

SPN	U011
HGNC	15605
MGI	1925723
PubMed	21669874
RGD	708436
UniProt	Q86WV1
Wiki	SKAP1

Src kinase-associated phosphoprotein 1 is a T cell adaptor 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 and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adaptor protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins. 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 and in regulating ERK activation in T-cells .

Reference

"Molecular cloning of SKAP55, a novel protein that associates with p59fyn in human T-lymphocytes."
J. Biol. Chem. 272:16077-16080(1997) [PubMed] [Europe PMC] [Abstract]

"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130."
J. Biol. Chem. 273:25789-25795(1998) [PubMed] [Europe PMC] [Abstract]

"FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells."
Proc. Natl. Acad. Sci. U.S.A. 95:8779-8784(1998) [PubMed] [Europe PMC] [Abstract]

"SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55."
EMBO J. 19:2889-2899(2000) [PubMed] [Europe PMC] [Abstract]

"SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation."
J. Biol. Chem. 277:40420-40427(2002) [PubMed] [Europe PMC] [Abstract]

"SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription."
Mol. Cell. Biol. 22:2673-2686(2002) [PubMed] [Europe PMC] [Abstract]

"SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates."
Nat. Immunol. 4:366-374(2003) [PubMed] [Europe PMC] [Abstract]

"Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells."
J. Biol. Chem. 280:23576-23583(2005) [PubMed] [Europe PMC] [Abstract]

"An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R."
J. Exp. Med. 201:1733-1739(2005) [PubMed] [Europe PMC] [Abstract]

"Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein."
J. Biol. Chem. 281:13743-13750(2006) [PubMed] [Europe PMC] [Abstract]

"The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1."
Mol. Cell. Biol. 26:7130-7144(2006) [PubMed] [Europe PMC] [Abstract]

"SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1."
Mol. Immunol. 45:510-522(2008) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Structural basis for the dimerization and phosphoinositide specificity of the Src kinase-associated phosphoproteins SKAP55 and SKAP-HOM."
Submitted (JUL-2005) to the PDB data bank