Fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating.

Ottilie, Sabine; Miller, Peter J.; Johnson, Douglas I.; Creasy, Caretha L.; Sells, Mary Ann; Bagrodia, Shubha; Forsburg, Susan L.; Chernoff, Jonathan

doi:10.1002/j.1460-2075.1995.tb00278.x

Cited by 150 publications

(193 citation statements)

References 53 publications

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“…The speci®city of the antiserum was veri®ed, since immunoprecipitation was blocked when the antiserum was preincubated with recombinant GST-KHS ( Figure 3a). This antiserum was also able to speci®cally immunoprecipitate a 95 kD protein from metaboli- (Katz et al, 1994;Creasy and Cherno , 1995;Cvrckova et al, 1995;Leberer et al, 1992;Ramer and Davis, 1993;Freisen et al, 1994;Marcus et al, 1995;Bagrodia et al, 1995;Knaus et al, 1995;Manser et al, 1994Martin et al, 1995;Ottilie et al, 1995). Catalytic domains are boxed.…”

Section: Resultsmentioning

confidence: 99%

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

Tung

Blenis

1997

Oncogene

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STE20-homologous proteins have been implicated in mammalian MAP kinase pathways as important transducers of signals from p21 family GTPases. We have cloned a novel STE20 family member, which we call KHS for kinase homologous to SPS1/STE20, that encodes a kinase of 95 kD which is expressed in a variety of tissues. Transiently expressed fusion protein GST-KHS exhibits phosphotransferase activity toward a panel of test substrates, including myelin basic protein (MBP), which is phosphorylated by all known STE20 homologues. KHS is most closely related to another human STE20, GC kinase (74% similar in the catalytic domain), which has recently been placed upstream of the stress-activated MAP kinases (SAPKs/JNKs. KHS also activates JNK in transient coexpression experiments, suggesting a role for KHS in the stress response of ®broblasts. Characterization and comparison of the regulation of these two kinases will be important in elucidating MAP kinase signalling cascades.

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Section: Resultsmentioning

confidence: 99%

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

Tung

Blenis

1997

Oncogene

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“…The Sequences were aligned using the CLUSTAL program of the PC GENE package. Proteins are S. cerevisiae Cla4 (Cvrcková et al, 1995), S. cerevisiae Ste20 (Leberer et al, 1992), rat p65 PAK (Manser et al, 1994) and S. pombe Pak1 (Ottilie et al, 1995). The PH consensus is also aligned (Musacchio et al, 1993 Skm1p is not redundant with Ste20p or Cla4p…”

Section: Disruption Of the Skm1 Gene Is Non-lethalmentioning

confidence: 99%

“…Cla4p has been shown to be required for cytokinesis and to perform essential functions in cell growth that overlap with those of Ste20p (Cvrcková et al, 1995). Ste20p is known to act as a MAPKKK activator in the pheromonetransduction pathway coupling both the receptor-activated heterotrimeric G protein and Cdc42p to a MAP kinase cascade (Simon et al, 1995); this points to a similar function for Ste20/PAK kinases in yeasts and other organisms (Ottilie et al, 1995;Vojtek and Cooper, 1995). Indeed, the recently identified human PAK isoform, hPAK1, has been shown to be the GTPase effector which links Cdc42 and Rac1 to the JNK MAP kinase pathway (Brown et al, 1996).…”

Section: Introductionmentioning

confidence: 96%

**Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK‐like protein kinase**

Martı́n

Mendoza

Rodrı́guez-Pachón

et al. 1997

Molecular Microbiology

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SummarySte20/PAK serine/threonine protein kinases have been suggested as playing essential roles in cell signalling and morphogenesis as potential targets of Cdc42 and Rac GTPases. We have isolated and characterized the Saccharomyces cerevisiae SKM1 gene, which codes for a novel member of this family of protein kinases. The amino acid sequence analysis of Skm1p revealed the presence of a PH domain and a putative p21-binding domain near its amino terminus, suggesting its involvement in cellular signalling or cytoskeletal functions. However, deletion of SKM1 produced no detectable phenotype under standard laboratory conditions. Moreover, disruption of each of the two other S. cerevisiae Ste20/PAK-like kinase-encoding genes, STE20 and CLA4, in skm1 backgrounds, showed that Skm1p is not redundant with Ste20p or Cla4p. Interestingly, overexpression of SKM1 led to morphological alterations, indicating a possible role for this protein in morphogenetic control. Furthermore, overproduction of Skm1p lacking its N-terminus caused growth arrest. This effect was also seen when similarly truncated versions of Ste20p or Cla4p were overexpressed. We further observed that overproduction of this C-terminal fragment of Skm1p complements the mating defect of a ste20 mutant strain. These results suggest that the N-terminal domains of S. cerevisiae Ste20/ PAK-like protein kinases share a negative regulatory function and play a role in substrate specificity.

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“…The disruption of the cdc42 gene is lethal to fission yeast, and the cdc42 mutants exhibit abnormal morphological phenotypes (9). Genetic and molecular studies suggest that a Dbl homology domain-containing Scd1 protein functions as the guanine nucleotide exchange factor for the fission yeast Cdc42 protein and that the GTP-bound Cdc42 activates Ste20 homologous kinase 1 (Shk1) 1 (12)(13)(14)(15). The fission yeast Shk1 belongs to the family of the p21-activated kinase (PAK), which is a highly conserved serine/ threonine kinase activated by the Cdc42/Rac protein.…”

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confidence: 99%

The Cdc42 Binding and Scaffolding Activities of the Fission Yeast Adaptor Protein Scd2

Endo¹,

Shirouzu²,

Yokoyama³

2003

Journal of Biological Chemistry

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The small GTP-binding protein Cdc42, the guanine nucleotide exchange factor Scd1, the p21-activated kinase Shk1, and the adaptor protein Scd2 are involved in the Cdc42-dependent signaling cascade in fission yeast. In the present study, we analyzed the Cdc42 binding and scaffolding activities of Scd2 by co-precipitation assays. We found that two SH3-containing regions, amino acid residues 1-87 (CB1 (Cdc42-binding region 1)) and 110 -266 (CB2), of Scd2 can bind to the GTP-bound form of Cdc42. CB2 is cryptic because of the intramolecular binding between the SH3 domain in CB2 (SH3(C)) and the PX domain and binds to Cdc42 only when the Scd2 PB1 domain binds to the PC motif-containing region (residues 760 -872) of Scd1. This CB2⅐Cdc42 association, which would stabilize the open configuration of Scd2, enables the SH3(C) domain to bind to the polyproline motif of Shk1. We also found that the GTP-bound form of Cdc42 binds to the CRIB motif of Shk1 more strongly than to Scd2. Thus, Scd2 functions as a scaffold to form a protein complex, and the GTP-bound Cdc42 might be transferred effectively from the upstream activator Scd1 to the downstream effector Shk1 via Scd2.

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Fission yeast pak1+ encodes a protein kinase that interacts with Cdc42p and is involved in the control of cell polarity and mating.

Cited by 150 publications

References 53 publications

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

**Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK‐like protein kinase**

The Cdc42 Binding and Scaffolding Activities of the Fission Yeast Adaptor Protein Scd2

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