Substrate specificity of protein tyrosine phosphatase: differential behavior of SHP-1 and SHP-2 towards signal regulation protein SIRPalpha1.
The substrate specificity of catalytic domains and the activation of full length protein tyrosine phosphatases, SHP-1 and SHP-2 have been investigated using synthetic phosphotyrosyl peptides derived from SIPRalpha1. We found that the catalytic domains of SHP-1 and SHP-2 exhibit different substrate specificity towards a longer trideca-peptide pY(469+3) ((-7)RPEDTLTpYADLDM(+5)) and not to the shorter decapeptide pY(469) ((-5)EDTLTpYADLD(+4)), the former being the substrate of SHP-2 only. Furthermore, the activation of full-length SHP-1 and not the SHP-2 by the deca/trideca-peptides suggested SIRPalpha 1 to be possibly acting as both an upstream activator and a substrate for SHP-1, and merely as the downstream substrate for SHP-2 in signaling events.
Mishra
Ashwini K
AK
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
Zhang
Aihua
A
Niu
Tianqi
T
Yang
Jian
J
Liang
Xiaoshan
X
Zhao
Zhizhuang Joe
ZJ
Zhou
G Wayne
GW
D000943:Antigens, Differentiation; D020134:Catalytic Domain / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011971:Receptors, Immunologic; D013379:Substrate Specificity
D000943:Antigens, Differentiation; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D009842:Oligopeptides; D011971:Receptors, Immunologic; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases