Proteiinityrosiinikinaasien ja tyrosiinifosfataasien tasapainossa on PTN tärkeä osatekijä.

https://www.pnas.org/content/103/47/17795
The balanced activities of tyrosine kinases (= fosforylases)  and tyrosine phosphatases dynamically regulate the steady-state levels of tyrosine phosphorylation of key proteins essential for many important cellular functions.
 The regulated disruption of this balance through growth factor and/or cytokine-activated receptor-transduced signals is an important mechanism of signal transduction but, when deregulated, is a mechanism frequently underlying different diseases and a major feature in the pathogenesis of many human malignancies (1).
 An important gap, however, is in understanding the mechanism of how different pathways and systems are coordinated to initiate the many different cellular functions required for normal cellular homeostasis, proliferation, and differentiation of cells.

(Kommenttini: Pleiotrofiinin osuus tämän  fundamentaalisen fosforylaation eöi  fosfaatin lisäämisen ja  fosfaatin poistamisen   tasapainon säätelyssä keskiössä! Artikkeli vuodelta 2006 taustana: )

Pleiotrophin disrupts calcium-dependent homophilic cell–cell adhesion and initiates an epithelial–mesenchymal transition

P. Perez-Pinera, S. Alcantara, T. Dimitrov, J. A. Vega, and T. F. Deuel

PNAS November 21, 2006 103 (47) 17795-17800; https://doi.org/10.1073/pnas.0607299103

Abstract

Regulation of the levels of tyrosine phosphorylation is essential to maintain the functions of proteins in different signaling pathways and other cellular systems, but how the steady-state levels of tyrosine phosphorylation are coordinated in different cellular systems to initiate complex cellular functions remains a formidable challenge. The receptor protein tyrosine phosphatase (RPTP)β/ζ is a transmembrane tyrosine phosphatase whose substrates include proteins important in intracellular and transmembrane protein-signaling pathways, cytoskeletal structure, cell–cell adhesion, endocytosis, and chromatin remodeling. 

Pleiotrophin (PTN the protein and Ptn the gene) is a ligand for RPTPβ/ζ;

 PTN inactivates RPTPβ/ζ, leaving unchecked the continued endogenous activity of tyrosine kinases that increase phosphorylation of the substrates of RPTPβ/ζ at sites dephosphorylated by RPTPβ/ζ in cells not stimulated by PTN.

 Thus, through the regulation of the tyrosine phosphatase activity of RPTPβ/ζ, the PTN/RPTPβ/ζ signaling pathway coordinately regulates the levels of tyrosine phosphorylation of proteins in many cellular systems. 

We now demonstrate that PTN disrupts cytoskeletal protein complexes, ablates calcium-dependent homophilic cell–cell adhesion, stimulates ubiquitination and degradation of N-cadherin, reorganizes the actin cytoskeleton, and induces a morphological epithelial–mesenchymal transition (EMT) in PTN-stimulated U373 cells. 

The data suggest that increased tyrosine phosphorylation of the different substrates of RPTPβ/ζ in PTN-stimulated cells alone is sufficient to coordinately stimulate the different functions needed for an EMT; it is possible that PTN initiates an EMT in cells at sites where PTN is expressed in development and in malignant cells that inappropriately express Ptn.

• receptor protein tyrosine phosphataseβ/ζ
• glioblastoma
• cadherin
• β-catenin
• cytoskeleton

 The balanced activities of tyrosine kinases and tyrosine phosphatases dynamically regulate the steady-state levels of tyrosine phosphorylation of key proteins essential for many important cellular functions. The regulated disruption of this balance through growth factor and/or cytokine-activated receptor-transduced signals is an important mechanism of signal transduction but, when deregulated, is a mechanism frequently underlying different diseases and a major feature in the pathogenesis of many human malignancies (1). An important gap, however, is in understanding the mechanism of how different pathways and systems are coordinated to initiate the many different cellular functions required for normal cellular homeostasis, proliferation, and differentiation of cells.

 The diverse substrates of the receptor protein tyrosine phosphatase (RPTP)β/ζ (2) include β-catenin (2), β-adducin (3, 4), Fyn (5), GIT1/Cat-1 (6), and P190RhoGAP (7), indicating that RPTPβ/ζ is promiscuous in substrate specificity, but through its activity, is critically positioned to coordinately regulate the steady-state levels of tyrosine phosphorylation of proteins in different signaling networks and cellular systems. 

Pleiotrophin (PTN the protein and Ptn the gene) is a secreted, highly conserved cytokine (8, 9) that signals through inactivation of RPTPβ/ζ; as a consequence, PTN coordinately increases tyrosine phosphorylation of the many substrates of RPTPβ/ζ through persistent activity of the tyrosine kinases that phosphorylate the same sites that are dephosphorylated by RPTPβ/ζ in cells not stimulated by PTN.

 The diverse substrates regulated through the PTN/RPTPβ/ζ signaling pathway thus are likely to account for the diverse functions signaled by PTN in different cellular systems and in the different malignant cell lines with inappropriate expression of Ptn (10).