Orchestrating cellular signaling pathways—the cellular “conductor” protein tyrosine phosphatase interacting protein 51 (PTPIP51)

Brobeil, Alexander; Dietel, Eric; Gattenlöhner, Stefan; Wimmer, Monika

doi:10.1007/s00441-016-2508-5

Cited by 9 publications

(13 citation statements)

References 91 publications

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“…A probable mechanism explaining the described altered interaction of PTPIP51 with its endogenous interactome might be an allosteric switch within the PTPIP51 protein structure. PTPIP51 exerts its function by specific binding sites [ 2 , 32 ]. These binding sites can either be exposed or concealed by LDC-3, thus facilitating or impairing interactions.…”

Section: Discussionmentioning

confidence: 99%

Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

et al. 2017

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Protein–protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein–protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein–protein interactions of protein tyrosine phosphatase interacting protein 51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is now available. Therefore, LDC-3 allows for the studying of the regulation of the endogenous interactome by modulating PTPIP51 binding capacity. Small interfering ribonucleic acid (siRNA) experiments show that the modification in PTPIP51 binding capacity is induced by LDC-3. Application of LDC-3 annuls the known regulatory phosphorylation mechanisms for PTPIP51 and consequently, significantly alters the assembly of the PTPIP51 associated protein complexes. The treatment of human keratinocytes (HaCaT cells) with LDC-3 induces an altered protein–protein interaction profile of the endogenous interactome of PTPIP51. In addition, LDC-3 stabilizes PTPIP51 within a mitogen activated protein kinase (MAPK) complex composed of Raf-1 and the scaffold protein 14-3-3, independent of the phosphorylation status of PTPIP51. Of note, under LDC-3 treatment the regulatory function of the PTP1B on PTPIP51 fails to impact the PTPIP51 interaction characteristics, as reported for the HaCaT cell line. In summary, LDC-3 gives the unique opportunity to directly modulate PTPIP51 in malignant cells, thus targeting potential dysregulated signal transduction pathways such as the MAPK cascade. The provided data give critical insights in the therapeutic potential of PTPIP51 protein interactions and thus are basic for possible targeted therapy regimens.

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Section: Discussionmentioning

confidence: 99%

Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

et al. 2017

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“…One of the crucial spots for this regulation is the tyrosine 176 residue of PTPIP51 [ 9 , 10 , 11 ]. Its phosphorylation results in a break-up of the PTPIP51/14-3-3β/Raf-1 complex and hence the stimulation of the MAPK signaling is omitted [ 8 , 9 , 11 , 12 ]. The phosphorylation of the tyrosine 176 residue is under the control of the EGFR and other kinases, such as the cellular sarcoma kinase (c-Src) [ 8 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Its phosphorylation results in a break-up of the PTPIP51/14-3-3β/Raf-1 complex and hence the stimulation of the MAPK signaling is omitted [ 8 , 9 , 11 , 12 ]. The phosphorylation of the tyrosine 176 residue is under the control of the EGFR and other kinases, such as the cellular sarcoma kinase (c-Src) [ 8 , 10 , 11 , 12 ]. Dephosphorylation is mainly performed by PTP1B [ 9 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…The phosphorylation of the tyrosine 176 residue is under the control of the EGFR and other kinases, such as the cellular sarcoma kinase (c-Src) [ 8 , 10 , 11 , 12 ]. Dephosphorylation is mainly performed by PTP1B [ 9 , 11 , 12 ]. Another important phosphorylation site of PTPIP51 is the serine 212 residue.…”

Section: Introductionmentioning

confidence: 99%

“…Up to now, we assume, that the cleft represents a binding site for the Raf kinases [ 9 ]. Contrary to the interaction inhibiting tyrosine 176 residue, phosphorylation of the serine 212 residue leads to an augmentation of the interaction with Raf-1 via 14-3-3β [ 7 , 8 , 9 , 12 ]. Besides the cleft, PTPIP51 protein structure contains tetratricopeptide domains, which are known to serve as binding sites for protein-protein interactions [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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The Importance of the Right Framework: Mitogen-Activated Protein Kinase Pathway and the Scaffolding Protein PTPIP51

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The protein tyrosine phosphatase interacting protein 51 (PTPIP51) regulates and interconnects signaling pathways, such as the mitogen-activated protein kinase (MAPK) pathway and an abundance of different others, e.g., Akt signaling, NF-κB signaling, and the communication between different cell organelles. PTPIP51 acts as a scaffold protein for signaling proteins, e.g., Raf-1, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her2), as well as for other scaffold proteins, e.g., 14-3-3 proteins. These interactions are governed by the phosphorylation of serine and tyrosine residues of PTPIP51. The phosphorylation status is finely tuned by receptor tyrosine kinases (EGFR, Her2), non-receptor tyrosine kinases (c-Src) and the phosphatase protein tyrosine phosphatase 1B (PTP1B). This review addresses various diseases which display at least one alteration in these enzymes regulating PTPIP51-interactions. The objective of this review is to summarize the knowledge of the MAPK-related interactome of PTPIP51 for several tumor entities and metabolic disorders.

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Orchestrating cellular signaling pathways—the cellular “conductor” protein tyrosine phosphatase interacting protein 51 (PTPIP51)

Cited by 9 publications

References 91 publications

Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

Altered Protein Interactions of the Endogenous Interactome of PTPIP51 towards MAPK Signaling

The Importance of the Right Framework: Mitogen-Activated Protein Kinase Pathway and the Scaffolding Protein PTPIP51

Interplay of mitochondria-associated membrane proteins and autophagy: Implications in neurodegeneration

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