Pleckstrin homology- -domain

Ferguson, K.M., et al. Structure of the high affinity complex of inositol triphosphate with a phospholipase C pleckstrin homology domain. Celt 83 1037-1046, 1995. 

Pleckstrin homology domain (PH-domain) was first identified at the amino and carboxyl termini of a haematopoietic protein called pleckstrin. PH-domain, a protein region of approximately 120 amino acids, by binding to phosphatidylinositol lipids of the biological membranes induces the translocation of the PH-domain containing protein to membrane compartment. Various PH-domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring. 

PH Pleckstrin homology domain Binding to membrane phospholipids, such as phosphoinositides... 

Platinum Complexes Pleckstrin Homology Domain Plexins PMF... 

Lietzke, S. E., Bose, S., Cronin, T. et al. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol. Cell 6 385-394,2000. 

R. G., Huber, H.E. Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. 

Takeuchi H, Kanematsu T, Misumi Y, et al. Distinct specificity in the binding of inositol phosphates by pleckstrin homology domains of pleckstrin, RAC-protein kinase, diacylglycerol kinase and a new 130 kDa protein. Biochem Biophys Acta 1997 1359(3) 275-285. 

The structural element of PARK that interacts specifically with the Py-complex is localized in the C-terminal third of the PARK seqimce (Inglese et al., 1994). It possesses the characteristics of an independently folding protein domain and is ranked with the pleckstrin homology domains (PH domains). The PH domains are protein modules (see Chapter 8), foimd in many proteins, that by binding of inositol lipids (see Chapter 6) mediate protein-membrane interactions. 

The central function of Ptdlns(3,4,5)P3 is to bind to pleckstrin homology domains (PH domains) of signal proteins. PH domains are found as independent protein modules in many signal proteins (see Chapter 8.2.4) that mediate protein-lipid and possibly also protein-protein interactions. Ptdlns(3,4,5)P3 formed by P13-kinase serves to recruit signal molecules next in sequence to the membrane and to involve them in signal conduction. In addition, Ptdlns(3,4,5)P3 can also bring about an allosteric activation of its effector proteins. 

Fig. 8.9. Crosslinking of signal proteins with the help of protein modnles. A hypothetical protein is shown which contains SH2, SH3, PTB and PH domains. Recognition of phosphotyrosine residues occurs with the help of SH2 or PTB domains SH3 domains bind to proline-rich sequences (Pro in Protein 3) whilst the pleckstrin homology domains (PH domains) mediate binding to phosphatidyl-inositol-phosphates (PtdInsP) in the membrane. In an idealized scheme, the modular protein can associate several proteins (Protein 1 - Protein 3) and mediate interactions between these proteins (shown as broken arrows). The PH domain helps to recruit the complex to the cell membrane favoring interactions with other membrane-associated proteins (Protein X).

Fig. 8.20. Modular composition of adaptor proteins. Adaptor proteins do not show any enzyme activity of their own, but rather they contain protein modules which help to bind signal proteins into signal pathways. IRS-1 insulin receptor substrate 1 PTB phosphotyrosine binding domain PH pleckstrin homology domain P phosphotyrosine-containing binding site for SH2 or PTB domains HLH helrx-loop-hehx DNA binding motif...

Fig. 9.7. Domain structure of pl20-GAP. The functional domains of pl20-GAP are shown in linear form. PH pleckstrin homology domain SH Sarc homology domain A2 possibly Ca -dependent phospholipid binding motif 1,2,3, conserved sequences characteristic for GTPase-sti-mulating activity.

Fig. 9.8. Domain structure of mSos. The mSos-1 protein of mammals possesses a pleckstrin homology domain (PH), a Pro-rich domain for interaction with Grb2 and a catalytic domain with three sequence motifs (1,2,3) characteristic for Ras GEFs.

Kikkawa, S. Yoshida, N. Nakagawa, M. Iwasa, T. Tsuda, M. A novel rhodopsin kinase in Octopus photoreceptor possesses a pleckstrin homology domain and is activated by C protein y-subunits. J. Biol. Chem., 273, 7441-7447 (1998)... 

W643A <3> (<3> residue of the PH domain, mutation completely abolishes )8-ARK activity and activation by the G protein /3y-subunit [17]) [17] Additional information <3> (<3> effects of mutations in the pleckstrin homology domain of /1-ARK on activity, Ala-insertion following Trp-643 completely abolishes /I-ARK activity and activation by the G protein )8y-sub-unit [17]) [17]... 

Touhara, K. Effects of mutations in pleckstrin homology domain on adrenergic receptor kinase activity in intact cells. Biochem. Biophys. Res. Commun., 252, 669-674 (1998)... 

Touhara, K. Binding of multiple ligands to pleckstrin homology domain regulates membrane translocation and enzyme activity of -adrenergic receptor kinase. FEBS Lett., 417, 243-248 (1997)... 

Rebecchi, M. J., and Scarlata, S. (1998). Pleckstrin homology domains A common fold with diverse functions. Annu. Rev. Biophys. Biomol. Struct. 27, 503-528. 

Wang, D. S., Miller, R., Shaw, R., and Shaw, G. (1996). The pleckstrin homology domain of human beta I sigma II spectrin is targeted to the plasma membrane in vivo. Biochem. Biophys. Res. Commun. 225, 420—426. 

Zhang, P., Talluri, S., Deng, H., Branton, D., and Wagner, G. (1995b). Solution structure of the pleckstrin homology domain of Drosophila beta-spectrin. Structure 3, 1185-1195. 

Holz RW, Hlubek MD, Sorensen SD et al (2000) A pleckstrin homology domain specific for phosphatidylinositol 4, 5-bisphosphate (PtdIns-4,5-P2) and fused to green fluorescent protein identifies plasma membrane PtdIns-4,5-P2 as being important in exocytosis. J Biol Chem 275 17878-85... 

Andjelkovic, M., Jakubowicz, T., Cron, P., Ming, X. F., Han,J. W., and Hemmings, B. A. (1996). Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc. Natl. Acad. Sci. USA 93, 5699-5704. 

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