PH Domains

Lemmon, Mark A.; Keleti, David

doi:10.1002/3527603611.ch17

Cited by 4 publications

(11 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This segment possesses the sequence signatures (Fig. 1B) found in well characterized PH domains, even though PH domains in general can share as little as 10%-15% amino acid identity (Lemmon and Keleti 2005). In particular, the N-terminal portion of the presumptive PH domain in Ste5 contains basic residues situated at positions that are equivalent to those that mediate phosphoinositide binding and membrane targeting in crystal structures of other PH domains (Fig.…”

Section: A Candidate Ph Domain In Ste5mentioning

confidence: 98%

“…A hallmark of many PH domains (but far from all) is the ability to bind specific phosphoinositides in vitro (Lemmon and Keleti 2005). To determine whether the Ste5 PH domain binds phosphoinositides and whether the phenotypes of the mutants correlate with their phosphoinositide-binding capability, we used three independent methods to measure the association of the isolated Ste5 PH domain with these lipids.…”

Section: Ste5 Ph Domain Binds Phosphoinositides In Vitromentioning

confidence: 99%

“…However, as expected for authentic binding, the amount of vesicle- cerevisiae Ste5 PH domain with selected mammalian PH domains. Secondary structure elements (green arrows, ␤-strands; blue cylinder, ␣-helix) depict those in the crystal structure of the PLC␦1 PH domain (Lemmon and Keleti 2005). Basic residues in the ␤1-␤2 loop and the conserved Trp in the C-terminal helix are highlighted (bold).…”

Section: Ste5 Ph Domain Binds Phosphoinositides In Vitromentioning

confidence: 99%

“…Bem1, an SH3 domain-containing adaptor protein, has an internal Phox-homology (PX) domain, and PX domains can bind phosphoinositides (Sato et al 2001). Cdc24, the guanine nucleotide exchange factor (GEF) for Cdc42, has an internal pleckstrin-homology (PH) domain, and PH domains can also bind phosphoinositides (for review, see Lemmon and Keleti 2005).…”

mentioning

confidence: 99%

“…However, some sequence analysis algorithms predict that Ste5 contains a PH domain. We suspected that the candidate PH domain might be highly relevant to Ste5 function because some PH domains can associate with both phosphoinositides and G␤␥ (Lemmon and Keleti 2005). Recent genome-wide analysis of Saccharomyces cerevisiae PH domains relied on the SMART database, which did not pinpoint Ste5 .…”

mentioning

confidence: 99%

See 4 more Smart Citations

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain

Garrenton¹,

Young²,

Thorner³

2006

Genes Dev.

View full text Add to dashboard Cite

Ste5, the prototypic mitogen-activated protein kinase (MAPK) scaffold protein, associates with plasma membrane-tethered G␤␥ freed upon pheromone receptor occupancy, thereby initiating downstream signaling. We demonstrate that this interaction and membrane binding of an N-terminal amphipathic ␣-helix (PM motif) are not sufficient for Ste5 action. Rather, Ste5 contains a pleckstrin-homology (PH) domain (residues 388-518) that is essential for its membrane recruitment and function. Altering residues (R407S K411S) equivalent to those that mediate phosphoinositide binding in other PH domains abolishes Ste5 function. The isolated PH domain, but not a R407S K411S derivative, binds phosphoinositides in vitro. Ste5(R407S K411S) is expressed normally, retains G␤␥ and Ste11 binding, and oligomerizes, yet is not recruited to the membrane in response to pheromone. Artificial membrane tethering of Ste5(R407S K411S) restores signaling. R407S K411S loss-of-function mutations abrogate the constitutive activity of gain-of-function Ste5 alleles, including one (P44L) that increases membrane affinity of the PM motif. Thus, the PH domain is essential for stable membrane recruitment of Ste5, and this association is critical for initiation of downstream signaling because it allows Ste5-bound Ste11 (MAPKKK) to be activated by membrane-bound Ste20 (MAPKKKK).[Keywords: Pheromone response; plasma membrane; mutants; yeast; Saccharomyces cerevisiae; Ste20] Supplemental material is available at http://www.genesdev.org.

show abstract

Section: A Candidate Ph Domain In Ste5mentioning

confidence: 98%

Section: Ste5 Ph Domain Binds Phosphoinositides In Vitromentioning

confidence: 99%

Section: Ste5 Ph Domain Binds Phosphoinositides In Vitromentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain

Garrenton¹,

Young²,

Thorner³

2006

Genes Dev.

View full text Add to dashboard Cite

show abstract

Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development

Yamada¹,

Nomura²,

Yamano³

et al. 2012

Gene

View full text Add to dashboard Cite

A novel approach for screening immunogenic proteins inPenicillium marneffeiusing the ÎAFMP1ÎAFMP2deletion mutant ofAspergillus fumigatus

Woo

Chong

Lau

et al. 2006

FEMS Microbiology Letters

View full text Add to dashboard Cite

Using serum from guinea-pigs immunized with a DeltaAFMP1DeltaAFMP2 deletion mutant of Aspergillus fumigatus to screen a cDNA library of A. fumigatus, we cloned a novel immunogenic 57-kDa protein in A. fumigatus. We also cloned its 55-kDa homologue in Penicillium marneffei, which was possibly related to amino acid biosynthesis and metabolism, with homologues present only in the subphylum Pezizomycotina of Ascomycota. The recombinant 55-kDa protein of P. marneffei reacted strongly with guinea-pig serum immunized with P. marneffei and with the sera of patients with P. marneffei infection. A similar approach could be applied to immunogenic protein screening in other microorganisms for serological diagnosis, epidemiological studies and the study of vaccines.

show abstract

PH Domains

Cited by 4 publications

References 112 publications

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain

Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development

A novel approach for screening immunogenic proteins inPenicillium marneffeiusing the ÎAFMP1ÎAFMP2deletion mutant ofAspergillus fumigatus

Contact Info

Product

Resources

About

PH Domains

Cited by 4 publications

References 112 publications

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain

Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain

Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development

A novel approach for screening immunogenic proteins inPenicillium marneffeiusing the ÎAFMP1ÎAFMP2deletion mutant ofAspergillus fumigatus

Contact Info

Product

Resources

About

A novel approach for screening immunogenic proteins inPenicillium marneffeiusing the ÎAFMP1ÎAFMP2deletion mutant ofAspergillus fumigatus