学术探索
学术期刊
新闻热点
数据分析
智能评审

Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5)

被引：43
作者：
Futter, M
Uematsu, K
Bullock, SA
Kim, Y
Hemmings, HC
Nishi, A
Greengard, P
Nairn, AC
机构：
[1] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA
[2] Cornell Univ, Weill Med Coll, Dept Anesthesiol, New York, NY 10021 USA
[3] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA
[4] Kurume Univ, Sch Med, Dept Physiol, Fukuoka 8300011, Japan
[5] Kurume Univ, Sch Med, Dept Pharmacol, Fukuoka 8300011, Japan
[6] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06508 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 09期
关键词：
actin; dendritic spines; protein phosphatase;
D O I：
10.1073/pnas.0409802102
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Spinophilin is a protein that binds to protein phosphatase-1 and actin and modulates excitatory synaptic transmission and dendritic spine morphology. We have identified three sites phosphorylated by ERK2 (Ser-15 and Ser-205) and cyclin-dependent PK 5 (Cdk5) (Ser-17), within the actin-binding domain of spinophilin. Cdk5 and ERK2 both phosphorylated spinophilin in intact cells. However, in vitro, phosphorylation by ERK2, but not by Cdk5, was able to modulate the ability of spinophilin to bind to and bundle actin filaments. In neurons and HEK293 cells expressing GFP-tagged variants of spinophilin, imaging studies demonstrated that introduction of a phospho-site mimic (Ser-15 to glutamate) was associated with increased filopodial density. These results support a role for spinophilin phosphorylation by ERK2 in the regulation of spine morphogenesis.
引用
收藏
页码：3489 / 3494
页数：6
相关论文
共 38 条
[1]   Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic spines [J].
Allen, PB ;
Ouimet, CC ;
Greengard, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (18) :9956-9961
[2]   The MAPK cascade is required for mammalian associative learning [J].
Atkins, CM ;
Selcher, JC ;
Petraitis, JJ ;
Trzaskos, JM ;
Sweatt, JD .
NATURE NEUROSCIENCE, 1998, 1 (07) :602-609
[3]   Mutation in the phosphorylation sites of MAP kinase blocks learning-related internalization of apCAM in Aplysia sensory neurons [J].
Bailey, CH ;
Kaang, BK ;
Chen, M ;
Martin, KC ;
Lim, CS ;
Casadio, A ;
Kandel, ER .
NEURON, 1997, 18 (06) :913-924
[4]   The identification of a second actin-binding region in spinophilin/neurabin II [J].
Barnes, AP ;
Smith, FD ;
VanDongen, HM ;
VanDongen, AMJ ;
Milgram, SL .
MOLECULAR BRAIN RESEARCH, 2004, 124 (02) :105-113
[5]  
Berman DE, 1998, J NEUROSCI, V18, P10037
[6]   Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons [J].
Bibb, JA ;
Snyder, GL ;
Nishi, A ;
Yan, Z ;
Meijer, L ;
Fienberg, AA ;
Tsai, LH ;
Kwon, YT ;
Girault, JA ;
Czernik, AJ ;
Huganir, RL ;
Hemmings, HC ;
Nairn, AC ;
Greengard, P .
NATURE, 1999, 402 (6762) :669-671
[7]   Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5 [J].
Bibb, JA ;
Chen, JS ;
Taylor, JR ;
Svenningsson, P ;
Nishi, A ;
Snyder, GL ;
Yan, Z ;
Sagawa, ZK ;
Ouimet, CC ;
Nairn, AC ;
Nestler, EJ ;
Greengard, P .
NATURE, 2001, 410 (6826) :376-380
[8]  
Crow T, 1998, J NEUROSCI, V18, P3480
[9]  
Dailey ME, 1996, J NEUROSCI, V16, P2983
[10]   Developmental regulation of spine motility in the mammalian central nervous system [J].
Dunaevsky, A ;
Tashiro, A ;
Majewska, A ;
Mason, C ;
Yuste, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (23) :13438-13443
1234