Pleckstrin homology (PH) domains and phosphoinositides

PH domains (pleckstrin homology domains) are the 11th most common domain in the human genome and are best known for their ability to target cellular membranes by binding specifically to phosphoinositides. Recent studies in yeast have shown that, in fact, this is a property of only a small fraction of the known PH domains. Most PH domains are not capable of independent membrane targeting, and those capable of doing so (approx. 33%) appear, most often, to require both phosphoinositide and non-phosphoinositide determinants for their subcellular localization. Several recent studies have suggested that small GTPases such as ARF family proteins play a role in defining PH domain localization. Some others have described a signalling role for PH domains in regulating small GTPases, although phosphoinositides may also play a role. These findings herald a change in our perspective of PH domain function, which will be significantly more diverse than previously supposed.

ARF GAP with Dual Pleckstrin Homology (PH) Domains

Encyclopedia of Signaling Molecules ◽

10.1007/978-3-319-67199-4_100255 ◽

2018 ◽

pp. 411-411

Keyword(s):

Pleckstrin Homology ◽

Ph Domains

Pleckstrin Homology (PH) Domains

Handbook of Cell Signaling ◽

10.1016/b978-0-12-374145-5.00136-4 ◽

2010 ◽

pp. 1093-1101 ◽

Cited By ~ 2

Author(s):

Mark A. Lemmon

Keyword(s):

Pleckstrin Homology ◽

Ph Domains

N Terminus of Sos1 Ras Exchange Factor: Critical Roles for the Dbl and Pleckstrin Homology Domains

Molecular and Cellular Biology ◽

10.1128/mcb.18.2.771 ◽

1998 ◽

Vol 18 (2) ◽

pp. 771-778 ◽

Cited By ~ 41

Author(s):

Xiaolan Qian ◽

William C. Vass ◽

Alex G. Papageorge ◽

Pieter H. Anborgh ◽

Douglas R. Lowy

Keyword(s):

Biological Activity ◽

Growth Factor ◽

Map Kinase ◽

Stable Complex ◽

Egf Receptors ◽

Pleckstrin Homology ◽

3T3 Cells ◽

N Terminus ◽

Ph Domains ◽

Nih 3T3

ABSTRACT We have studied the functional importance of the N terminus of mouse Sos1 (mSos1), a ubiquitously expressed Ras-specific guanine nucleotide exchange factor whose C-terminal sequences bind Grb-2. Consistent with previous reports, addition of a myristoylation signal to mSos1 (MyrSos1) rendered it transforming for NIH 3T3 cells and deletion of the mSos C terminus (MyrSos1-ΔC) did not interfere with this activity. However, an N-terminally deleted myristoylated mSos1 protein (MyrSos1-ΔN) was transformation defective, although the protein was stable and localized to the membrane. Site-directed mutagenesis was used to examine the role of the Dbl and pleckstrin homology (PH) domains located in the N terminus. When mutations in the PH domain were introduced into two conserved amino acids either singly or together in MyrSos1 or MyrSos1-ΔC, the transforming activity was severely impaired. An analogous reduction in biological activity was seen when a cluster of point mutations was engineered into the Dbl domain. The mitogen-activation protein (MAP) kinase activities induced by the various Dbl and PH mutants of MyrSos1 correlated with their biological activities. When NIH 3T3 cells were transfected with a myristoylated Sos N terminus, their growth response to epidermal growth factor (EGF), platelet-derived growth factor, lysophosphatidic acid or serum was greatly impaired. The dominant inhibitory biological activity of the N terminus correlated with its ability to impair EGF-dependent activation of GTP-Ras and of MAP kinase, as well with the ability of endogenous Sos to form a stable complex with activated EGF receptors. The N terminus with mutations in the Dbl and PH domains was much less inhibitory in these biological and biochemical assays. In contrast to wild-type Sos1, nonmyristoylated versions of Sos1-ΔN and Sos1-ΔC did not form a stable complex with activated EGF receptors. We conclude that the Dbl and PH domains are critical for Sos function and that stable association of Sos with activated EGF receptors requires both the Sos N and C termini.

Pleckstrin homology (PH) domains in signal transducton

Journal of Cellular Biochemistry ◽

10.1002/jcb.240560403 ◽

1994 ◽

Vol 56 (4) ◽

pp. 436-443 ◽

Cited By ~ 48

Author(s):

Evan Ingley ◽

Brian A. Hemmings

Keyword(s):

Pleckstrin Homology ◽

Ph Domains

Duet is a novel serine/threonine kinase with Dbl-Homology (DH) and Pleckstrin-Homology (PH) domains

Gene ◽

10.1016/s0378-1119(98)00605-2 ◽

1999 ◽

Vol 227 (2) ◽

pp. 249-255 ◽

Cited By ~ 28

Author(s):

Taro Kawai ◽

Hideki Sanjo ◽

Shizuo Akira

Keyword(s):

Pleckstrin Homology ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

Ph Domains

Signal-dependent membrane targeting by pleckstrin homology (PH) domains

Biochemical Journal ◽

10.1042/0264-6021:3500001 ◽

2000 ◽

Vol 350 (1) ◽

pp. 1 ◽

Cited By ~ 226

Author(s):

Mark A. LEMMON ◽

Kathryn M. FERGUSON

Keyword(s):

Membrane Targeting ◽

Pleckstrin Homology ◽

Ph Domains