GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA

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	GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA
	Liu, Q. R. ; Zhang, P. W. ; Lin, Z. C. ; Li, Q. F. ; Woods, A. S. ; Troncoso, J. ; Uhl, G. R. ; Li QF(李祺福)
刊名	http://dx.doi.org/10.1042/BJ20030128
	2004
关键词	INTEGRIN-LINKED KINASE CAMP-REGULATED PHOSPHOPROTEIN SITE-DIRECTED MUTAGENESIS MYOSIN PHOSPHATASE SMOOTH-MUSCLE CATALYTIC SUBUNIT NUCLEOPHOSMIN B23 CRYSTAL-STRUCTURE IN-VIVO PHOSPHORYLATION
英文摘要	The activities of PP1 (protein phosphatase 1), a principal cellular phosphatase that reverses serine/threonine protein phosphorylation, can be altered by inhibitors whose activities are themselves regulated by phosphorylation. We now describe a novel PKC (protein kinase C)-dependent PP1 inhibitor, namely GBPI (gut and brain phosphatase inhibitor). The shorter mRNA that encodes this protein, GBPI-1, is expressed in brain, stomach, small intestine, colon and kidney, whereas a longer GBPI-2 splice variant mRNA is found in testis. Human GBPI-1 mRNA encodes a 145-amino-acid, 16.5 kDa protein with pI 7.92. GBPI contains a consensus PP1-binding motif at residues 21-25 and consensus sites for phosphorylation by enzymes, including PKC, PKA (protein kinase A or cAMP-dependent protein kinase) and casein kinase II. Recombinant GBPI-1-fusion protein inhibits PP1 activity with IC50 = 3 nM after phosphorylation by PKC. Phospho-GBPI can even enhance PP2A activity by > 50% at submicromolar concentrations. Non-phosphorylated GBPI-1 is inactive in both assays. Each of the mutations in amino acids located in potential PP1-binding sequences, K21E + K22E and W25A, decrease the ability of GBPI-1 to inhibit PP1. Mutations in the potential PKC phosphoacceptor site T58E also dramatically decrease the ability of GBPI-1 to inhibit PP1. Interestingly, when PKC-phosphorylated GBPI-1 is further phosphorylated by PKA, it no longer inhibits PP1. Thus, GBPI-1 is well positioned to integrate PKC and PKA modulation of PP1 to regulate differentially protein phosphorylation patterns in brain and gut. GBPI, its closest family member CPI (PKC-potentiated PP1 inhibitor) and two other family members, kinase-enhanced phosphatase inhibitor and phosphatase holoenzyme inhibitor, probably modulate integrated control of protein phosphorylation states in these and other tissues.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65173]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Liu, Q. R.,Zhang, P. W.,Lin, Z. C.,et al. GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA[J]. http://dx.doi.org/10.1042/BJ20030128,2004.
APA	Liu, Q. R..,Zhang, P. W..,Lin, Z. C..,Li, Q. F..,Woods, A. S..,...&李祺福.(2004).GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA.http://dx.doi.org/10.1042/BJ20030128.
MLA	Liu, Q. R.,et al."GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA".http://dx.doi.org/10.1042/BJ20030128 (2004).