Phage Display Based Cloning of Proteins Interacting with the Cytoplasmic Tail of Membrane Immunoglobulins

Geisberger, Roland; Prlic, Martin; Achatz‐Straussberger, Gertrude; Oberndorfer, Iris; Luger, Elke; Lamers, Marinus C.; Crameri, Reto; Appenzeller, Ulrich; Wienands, Jürgen; Breitenbach, Michael; Ferreira, Fátima; Achatz, Gernot

doi:10.1080/1044667031000137584

Cited by 16 publications

(12 citation statements)

References 27 publications

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“…We have shown that the adaptor protein, the HPK1-interacting protein of 55 kDa, is involved in the kinase activation of HPK1 by TCR stimulation (28). A recent phage display analysis found that HPK1 interacts with the cytoplasmic tail of membrane immunoglobulins (29). Although phosphorylation (4,5,7,(15)(16)(17)(18)30) and caspase-mediated cleavage (19,22) have been implicated in the regulation of HPK1, the details of the in vivo regulation of HPK1 remain largely unknown.…”

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confidence: 99%

Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1

Zhou

Boomer

Tan

2004

Journal of Biological Chemistry

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Hematopoietic progenitor kinase 1 (HPK1) is a hematopoietic specific mammalian Ste20-like protein kinase and has been implicated in many cellular signaling pathways including T cell receptor (TCR) signaling. However, little is known about the in vivo regulation of HPK1. We present evidence that HPK1 is positively regulated by protein phosphatase 4 (PP4; also called PPX and PPP4), a serine/threonine phosphatase. We found that PP4 interacted with HPK1 and that the proline-rich region of HPK1 was necessary and sufficient for this interaction. We also found that PP4 had phosphatase activity toward HPK1 in vivo and that co-transfection of PP4 with HPK1 resulted in specific kinase activation of HPK1. Moreover, we found that the PP4-induced HPK1 kinase activation was accompanied by an increase in protein expression of HPK1. Pulse-chase analysis showed that PP4 increased the half-life of HPK1. Further studies showed that HPK1 was subject to regulation by ubiquitination and ubiquitin-targeted degradation and that PP4 inhibited HPK1 ubiquitination. In addition, we found that TCR stimulation enhanced the PP4-HPK1 interaction and that wild-type PP4 enhanced, whereas a phosphatase-dead PP4 mutant inhibited, TCR-induced activation of HPK1 in Jurkat T cells. Combined with the observation that PP4 enhanced HPK1-induced JNK activation, our studies identify PP4 as a positive regulator for HPK1 and the HPK1-JNK signaling pathway.

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confidence: 99%

Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1

Zhou

Boomer

Tan

2004

Journal of Biological Chemistry

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“…Different regulation of BCR signaling through the B cell coreceptor CD22 was reported to be dependent on the distinct cytoplasmic tails ( and ␥) of the mIg isotypes (31). Also, for the -isotype, signal transduction was proposed to be different from other isotypes, including interactions of the cytoplasmic tail with specific cellular proteins (6,32). Moreover, it was recently reported that IgE ϩ cells could directly interact and trigger degranulation, in an Ag-independent manner, with mast cell and basophils expressing the FcRI (33).…”

Section: Discussionmentioning

confidence: 99%

The Extracellular Membrane-Proximal Domain of Human Membrane IgE Controls Apoptotic Signaling of the B Cell Receptor in the Mature B Cell Line A20

Poggianella

Bestagno

Burrone

2006

The Journal of Immunology

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Ag engagement of BCR in mature B cells can deliver specific signals, which decide cell survival or cell death. Circulating membrane IgE+ (mIgE+) cells are found in extremely low numbers. We hypothesized that engagement of an εBCR in a mature isotype-switched B cell could induce apoptosis. We studied the role of the extracellular membrane-proximal domain (EMPD) of human mIgE upon BCR engagement with anti-Id Abs. Using mutants lacking the EMPD, we show that this domain is involved in controlling Ca2+ mobilization in immunoreceptors of both γ and ε isotypes, as well as apoptosis in signaling originated only from the εBCR. We mapped to the εCH4 ectodomain the region responsible for apoptosis in EMPD-deleted receptors. Ca2+ mobilization was not related to apoptotic signaling. This apoptotic pathway was caspase independent, involved ERK1/2 phosphorylation and was partially rescued by CD40 costimulation. We therefore conclude that the EMPD of human mIgE is a key control element of apoptotic signaling delivered through engagement of εBCR within the context of a mature B cell.

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“…HPK1 is activated by both EGF and PDGF stimulation where adaptor proteins are involved in mediating the localization of effector molecules to cell surface receptors [Anafi et al, 1997;Ling et al, 1999]. HPK1 also binds the cytoplasmic tail of IgE [Geisberger et al, 2002], but the functional significance of this interaction is unknown.…”

Section: Hpk1-mediated Cellular Signalingmentioning

confidence: 98%

Functional interactions of HPK1 with adaptor proteins

Boomer¹,

Tan²

2005

J of Cellular Biochemistry

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Hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) is a hematopoietic-specific mammalian STE20-like protein serine/threonine kinase, comprised of a STE20-like kinase domain in its N-terminus, four proline-rich motifs, a caspase cleavage site, and a distal C-terminal Citron homology domain. HPK1 is involved in many cellular signaling cascades that include MAPK signaling, antigen receptor signaling, apoptosis, growth factor signaling, and cytokine signaling. HPK1 binds many adaptor proteins including members of the Grb2 family, Nck family, Crk family, SLP-76 family, and actin-binding adaptors like HIP-55. HPK1 tyrosine phosphorylation and kinase activation depend on the presence of adaptor proteins. Adaptor proteins are required not only for linking HPK1 to cell surface receptors like the EGFR, but also for downstream gene transcription like NFAT, AP-1 and IL-2. The HPK1 association with Crk, CrkL, and HIP-55 mediate HPK1-dependent c-Jun N-terminal kinase (JNK) activation, while the association of HPK1 with SLP-76, Gads, CrkL, Grb2, and Grap affect T- and B-cell dependent gene transcription. Interestingly, HPK1 has been implicated in both increasing and decreasing NFAT, AP-1, and IL-2 gene transcription in T-cells where adaptor proteins play a key role. Lastly, HPK1 will phosphorylate Crk and CrkL, in vitro, which presents a novel possibility for the regulation of adaptor proteins and downstream signaling events.

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Phage Display Based Cloning of Proteins Interacting with the Cytoplasmic Tail of Membrane Immunoglobulins

Cited by 16 publications

References 27 publications

Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1

Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1

The Extracellular Membrane-Proximal Domain of Human Membrane IgE Controls Apoptotic Signaling of the B Cell Receptor in the Mature B Cell Line A20

Functional interactions of HPK1 with adaptor proteins

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