Psychiatry related information on Ptpra

• PTPalpha(-/-) and WT mice were tested for anxiety, swimming ability, spatial learning, cued learning, locomotor activity, and novel object recognition (NOR) [1].
• During Morris water maze (MWM) learning, PTPalpha(-/-) mice had increased latencies to reach the goal compared to WT on acquisition, but no memory deficit on probe trials [1].

High impact information on Ptpra

• Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha [2].
• In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra(-/-) mice [3].
• Receptor protein tyrosine phosphatase alpha is essential for hippocampal neuronal migration and long-term potentiation [3].
• PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration [4].
• FN-induced cytoskeletal rearrangement was retarded in PTP alpha-/- cells, with delayed filamentous actin stress fiber assembly and focal adhesion formation [4].

Chemical compound and disease context of Ptpra

• PTPalpha(-/-) mice showed decreased exploratory locomotor activity, but responded normally to a challenge dose of D-methamphetamine [1].

Biological context of Ptpra

• Although TCR-mediated tyrosine phosphorylation was apparently unaffected by the absence of PTPalpha, the long-term proliferative response of PTPalpha-/- thymocytes was reduced [5].
• Structural basis for inhibition of receptor protein-tyrosine phosphatase-alpha by dimerization [6].
• This explains why the substitutions eliminated PTPalpha transforming activity, even though PTPalpha interphase dephosphorylation of nonspecific substrates was only slightly decreased [7].
• Thus, in addition to increasing PTPalpha nonspecific catalytic activity, Ser180 and Ser204 phosphorylation (along with Tyr789 phosphorylation) regulates PTPalpha substrate specificity [7].
• Expression of receptor protein-tyrosine phosphatase alpha mRNA and protein during mouse embryogenesis [8].

Anatomical context of Ptpra

• Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts [9].
• Defects in PTP alpha-/- migration in a wound healing assay were associated with altered cell shape and focal adhesion kinase (FAK) phosphorylation [4].
• To examine the potential cellular functions and physiological substrates of PTPalpha, a potent phosphorothioate oligonucleotide-based antisense strategy was developed that specifically depleted endogenous PTPalpha from 3T3-L1 adipocytes [10].
• Thus the involvement of PTPalpha as an upstream regulator of NMDAR tyrosine phosphorylation was investigated in synaptosomes of wild-type and PTPalpha-null mice [11].
• In addition, these compounds inhibited PTPalpha-dependent cell spreading in NIH 3T3 cells at concentrations that were similar to their activity in biochemical assays [12].

Associations of Ptpra with chemical compounds

• Moreover, either a Ser-to-Ala substitution or serine dephosphorylation specifically eliminated the ability of PTPalpha to dephosphorylate and activate Src even during interphase [7].
• This occurred without change in the phosphorylation of PTPalpha at Tyr789, which is required for "phosphotyrosine displacement" during Src dephosphorylation [7].
• Significantly, replacing Gln(259) with a glycine almost turns PTPalpha into a PTP1B-like enzyme [13].
• Consistent with this observation, in vitro phosphatase assays using purified glutathione S-transferase fusion proteins demonstrated a preference for the transmembrane protein-tyrosine phosphatase-alpha over the cytosolic protein-tyrosine phosphatase-1B [14].
• Residue 259 in protein-tyrosine phosphatase PTP1B and PTPalpha determines the flexibility of glutamine 262 [15].

Enzymatic interactions of Ptpra

• CD45 could directly dephosphorylate PTPalpha in vitro [16].

Regulatory relationships of Ptpra

• Some PTPalpha is localized in lipid rafts of thymocytes, and raft-associated Fyn is specifically activated in PTPalpha-/- cells [5].

Other interactions of Ptpra

• Together, our results indicate that PTPalpha, likely located in lipid rafts, regulates the activity of raft Fyn [5].
• PTPalpha is not a Cbp/PAG phosphatase, because it is not required for Cbp/PAG dephosphorylation in unstimulated or anti-CD3-stimulated thymocytes [5].
• Protein kinase C delta induces Src kinase activity via activation of the protein tyrosine phosphatase PTP alpha [17].
• Functional interrelationships between PTPepsilon and PTPalpha and the mechanisms by which they regulate K(+) channels and Src were analyzed in vivo in mice lacking either or both PTPs [18].

Analytical, diagnostic and therapeutic context of Ptpra

• Reciprocal immunoprecipitations and assays detected p59(fyn) and an appropriate kinase activity in PTPalpha immunoprecipitates and PTPalpha and PTP activity in p59(fyn) immunoprecipitates [19].
• By using a novel set of PTP inhibitors and x-ray crystallography, we further provide evidence that Gln(259) in PTPalpha plays a dual role leading to restricted substrate recognition (directly via steric hindrance) and reduced catalytic activity (indirectly via Gln(262)) [13].

References