Phosphatases in disease

Many phosphatases are key in the development of pathological pathways where inhibition can reverse or delay the onset of human diseases.

Abnormal serine/threonine phosphatase activity has been linked with several diseases, including diabetes, cardiovascular disorders, cancer, and Alzheimer's disease. Therefore, the pharmacological manipulation of phosphatase activity is an attractive strategy for the treatment of such conditions.

Serine/Theonine phosphatases are metal-requiring enzymes that regulate many pathways involved in cell proliferation, programmed cell death (apoptosis), embryonic development, and cell differentiation. They are grouped into two gene families - the PPP and the PPM gene families, based on sequence analysis. 

Human Serine-threonine Phosphatase Graph

PPP Gene family

The PP1 subfamily is comprised of a catalytic subunit that interacts with several proteins including targeting subunits and inhibitor proteins.

The PP2A subfamily are heterotrimers comprised of a catalytic subunit and two regulatory subunits.

PPM Gene Family

This group corresponds to the PP2C enzymes, which are activated by high concentrations of magnesium. This subfamily is less well-studied than the PPP group, and little is known about their regulation.

 
 
Examples of popular knockout cell lines for studying Serine-threonine Phosphatase
AKAP1 AKAP11 AKAP9 ANKRD28 ANKRD44
ANKRD52 KIAA1244 BCL2L2 CD2BP2 CDC25C
CENPE CHCHD3 CHCHD6 CLCN7 CNST
CSMD1 CSRNP2 CTDNEP1 CTDSP1 CTDSP2
CTDSPL DDX31 DLG2 DZIP3 ELFN1
ELFN2 FARP1 FKBP15 ILKAP PDP1
PHLPP1 PHLPP2 PPEF1 PPM1A PPM1B
PPM1D PPM1E PPM1F PPM1G PPM1H
PPM1J PPM1K PPM1L PPM1M PPM1N
PPP1CA PPP1R13B PPP1R14A PPP1R14C PPP1R15A
PPP1R16A PPP1R16B PPP1R18 PPP1R26 PPP1R21
PPP1R32 PPP1R37 PPP1R3B PPP1R3D PPP1R3F
PPP1R9A PPP1R9B PPP2CB PPP2R1B PPP2R2B
PPP2R2C PPP2R2D PPP2R3A PPP2R5A PPP2R5B
PPP2R5C PPP2R5D PPP2R5E PPP3CA PPP3CB
PPP3CC PPP4R1 PPP4R2 PPP4R4 PPP5C
PPP6R1 PPP6R2 Sh6GLB1 TP53BP2 ZFYVE16
UBLCP1 PPP1R1A PPP1R14B