Structural highlights
Function
PTN22_MOUSE Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-492' residue. Dephosphorylates the immune system activator SKAP2 (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
C-terminal Src kinase (Csk) takes part in a highly specific, high affinity interaction via its Src homology 3 (SH3) domain with the proline-enriched tyrosine phosphatase PEP in hematopoietic cells. The solution structure of the Csk-SH3 domain in complex with a 25-residue peptide from the Pro/Glu/Ser/Thr-rich (PEST) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH3 domain. Three residues, Ala 40, Thr 42 and Lys 43, in the SH3 domain of Csk specifically recognize two hydrophobic residues, Ile 625 and Val 626, in the proline-rich sequence of the PEST domain of PEP. These two residues are C-terminal to the conventional proline-rich SH3 domain recognition sequence of PEP. This interaction is required in addition to the classic polyproline helix (PPII) recognition by the Csk-SH3 domain for the association between Csk and PEP in vivo. NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition.
A novel, specific interaction involving the Csk SH3 domain and its natural ligand.,Ghose R, Shekhtman A, Goger MJ, Ji H, Cowburn D Nat Struct Biol. 2001 Nov;8(11):998-1004. PMID:11685249[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cloutier JF, Veillette A. Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells. EMBO J. 1996 Sep 16;15(18):4909-18. PMID:8890164
- ↑ Ghose R, Shekhtman A, Goger MJ, Ji H, Cowburn D. A novel, specific interaction involving the Csk SH3 domain and its natural ligand. Nat Struct Biol. 2001 Nov;8(11):998-1004. PMID:11685249 doi:10.1038/nsb1101-998
