In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome. Both PHLPP1 and PHLPP2 are commonly deleted in human cancers, supporting a tumor suppressive role. Conversely, the levels of one isozyme, PHLPP1, are elevated in diabetes. Thus, mechanisms to correctly control PHLPP activity in cells are critical for normal cellular homeostasis. This review summarizes the known functions of PHLPP and its role in disease.
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Cover Image
Cover Image
Views of the Fc region of human immunoglobulin A (IgA) with interaction sites for key host receptors highlighted in the upper images, and those for bacterial IgA binding proteins in the lower ones. The remarkable co-localisation of these sites illustrates how various bacterial pathogens have co-opted sites on immunoglobulins as an effective means to block the elimination mechanisms which immunoglobulins normally trigger. See pp. 1651–1658 for further information. Image provided by J. Woof.
PHLPPing through history: a decade in the life of PHLPP phosphatases
Agnieszka T. Grzechnik, Alexandra C. Newton; PHLPPing through history: a decade in the life of PHLPP phosphatases. Biochem Soc Trans 15 December 2016; 44 (6): 1675–1682. doi: https://doi.org/10.1042/BST20160170
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