Proline-rich tyrosine kinase 2 regulates proliferation and differentiation of prostate cells.
Proline-rich tyrosine kinase 2 (Pyk2) expression in prostate epithelium inversely correlated with degree of malignancy of prostate cancers, thus the role of Pyk2 in the regulation of prostate cells proliferation and differentiation was investigate in PC3 cells. Pyk2 can be activated by canonic stimuli such as tumor necrosis factoralpha and lysophosphatidic acid (LPA) in PC3 cells, in addition, LPA stimulated Pyk2 phosphorylation also induced extracellular signal-regulated kinase 1 and 2 activation in these cells. Proliferation of PC3 cell clones (PC3-PKM) expressing a dominant negative kinase-defective Pyk2 mutant is consistently decreased in respect to that of wild type PC3 cells. In addition, PC3-PKM clones underwent total block cell proliferation upon treatment with dibutyryl cAMP. Finally, in the presence of sustained levels of intracellular cAMP, PC3-PKM cells, but not wild type PC3 cells, acquired a neuron-like morphology. Taken together our results suggest that Pyk2 plays a role in the regulation of prostate cell proliferation and, more interestingly, its expression may represents a sensitive marker of prostate state of differentiation.
Picascia
Antonietta
A
Dipartimento di Biologia e Patologia Molecolare e Cellulare 'Luigi Califano', Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Universita degli Studi di Napoli, 'Federico II' Via Pansini 5, 80131, Naples, Italy.
Stanzione
Rosita
R
Chieffi
Paolo
P
Kisslinger
Annamaria
A
Dikic
Ivan
I
Tramontano
Donatella
D
D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D051418:Focal Adhesion Kinase 2; D006801:Humans; D008246:Lysophospholipids; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha
D008246:Lysophospholipids; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2