Serine Phosphorylation-dependent Association of the Band 4.1-related Protein-tyrosine Phosphatase PTPH1 with 14-3-3 Protein

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 11/1997; 272(43):27281-7. DOI: 10.1074/jbc.272.43.27281
Source: PubMed


PTPH1 is a human protein-tyrosine phosphatase with homology to the band 4.1 superfamily of cytoskeletal-associated proteins.
PTPH1 was found to associate with 14-3-3β using a yeast two-hybrid screen, and its interaction could be reconstituted in vitro using recombinant proteins. Examination of the interaction between 14-3-3β and various deletion mutants of PTPH1 by two-hybrid
tests suggested that the integrity of the PTP is important for this binding. Although both PTPH1 and Raf-1 form complexes
with 14-3-3β, they appear to do so independently. Binding of 14-3-3β to PTPH1in vitro was abolished by pretreating PTPH1 with potato acid phosphatase and was greatly enhanced by pretreating with Cdc25C-associated
protein kinase. Thus the association between PTPH1 and 14-3-3β is phosphorylation-dependent. Two novel motifs RSLS359VE and RVDS853EP in PTPH1 were identified as major 14-3-3β-binding sites, both of which are distinct from the consensus binding motif RSXSXP recently found in Raf-1. Mutation of Ser359 and Ser853 to alanine significantly reduced the association between 14-3-3β and PTPH1. Furthermore, association of PTPH1 and 14-3-3β
was detected in several cell lines and was regulated in response to extracellular signals. These results raise the possibility
that 14-3-3β may function as an adaptor molecule in the regulation of PTPH1 and may provide a link between serine/threonine
and tyrosine phosphorylation-dependent signaling pathways.

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    • "More than 200 binding proteins have been reported to interact with the 14-3-3 proteins. These include receptors (Furlanetto et al., 1997; Wakui et al., 1997), kinases (Bonnefoy-Berard et al., 1995; Freed et al., 1994; Reuther et al., 1994), phosphatases (Conklin et al., 1995; Zhang et al., 1997), docking molecules (Garcia-Guzman et al., 1999; Ogihara et al., 1997), cell death regulators (Vincenz & Dixit, 1996; Zha et al., 1996) and oncogene products (Pallas et al., 1994; Reuther et al., 1994). One of the most well-studied binding partners of 14-3-3 proteins is Raf-1 (Fantl et al., 1994; Freed et al., 1994; Fu et al., 1994; Irie et al., 1994; Li et al., 1995; McPherson et al., 1999), a shared effector of both Ras and Rap proteins. "
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    • "The MITF-S173A mutation did not affect interaction with C-TAK1 in coimmunoprecipitation experiments , and endogenous 14-3-3 was not observed (Figure 6A, lane 4). These results are consistent with C-TAK1 as a protein kinase that can phosphorylate MITF and enhance interactions with 14-3-3, as has been reported for several other C-TAK1 substrates (Zhang et al., 1997; Peng et al., 1998; Muller et al., 2001, 2003). A consensus sequence for recognition of substrates by C-TAK1 has been developed based on sequence alignment and mutagenesis studies (Supplemental Figure 4) (Muller et al., 2003). "
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    • "In addition, the expression of several plant and mammalian isoforms is influenced by external stimuli like temperature, injury and different types of stress (Yaffe, 2002; Jarillo et al., 1994; de Vetten and Ferl, 1995; Chen et al., 1994; Kidou et al., 1993). Besides differences in expression patterns, there are several reports on isoform-specific interactions with 14-3-3 binding partners (Yaffe, 2002; Wakui et al., 1997; Craparo et al., 1997; Meller et al., 1996; Liu et al., 1997; Van Der Hoeven et al., 2000; Tang et al., 1998; Peng et al., 1997; Zhang et al., 1997; Kumagai et al., 1998; Kurz et al., 2000; Hashiguchi et al., 2000). However, many functions can be performed by all 14-3-3 isoforms. "
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