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MAPK Pathway

磷酸化是指把磷酸基团添加到分子特异氨基酸残基上的可逆过程。从功能上看，磷酸化充当的是一个能够激活、灭活或或调节蛋白功能的简单分子开关。添加和去除磷酸基团实现了对蛋白活性空间和时间上的控制。磷酸化受到一个激酶与磷酸化酶相互竞争而又相互依存的网络的严格控制，其中激酶为底物蛋白质提供磷酸基团，而磷酸化酶则会把它们从底物中移除。

丝裂原活化蛋白激酶 (MAPKs) 是一个高度保守而又广泛表达的、能够磷酸化许多不同靶底物的酶激酶家族。MAP-激酶则是一个更大的分层磷酸化级联反应的组成部分，该级联反应包括MAP2Ks和MAP3Ks。这种分层组织可以实现灵活性，从而通过激活MAP-激酶一个直接与其他功能蛋白相互作用的较小子集，使一系列的高阶激酶能够对刺激做出响应并控制细胞功能。

MAP-激酶几乎在所有细胞过程中都发挥着重要作用。MAPK依赖性磷酸化涉及调节细胞周期进程、分化、发育和凋亡的信号传导级联反应。

补充阅读：皮尔逊·G、罗宾逊·F、比尔斯·吉布森·T、Xu BE、克兰迪卡·M、伯曼·K、科布·MH (2001年4月)。《丝裂原活化蛋白(MAP) 激酶通路：调节和生理功能》。《内分泌学学报》版本22 (2): 153–83。 doi:10.1210/er.22.2.153. PMID 11294822

MAPK

MAPK14 (Mitogen-Activated Protein Kinase 14):

MAPK1 - ERK2:

MAPK10 (Mitogen-Activated Protein Kinase 10):

MAPK11 (Mitogen-Activated Protein Kinase 11):

MAPK12 (Mitogen-Activated Protein Kinase 12):

MAPK13 (Mitogen-Activated Protein Kinase 13):

MAPK14 (Mitogen-Activated Protein Kinase 14):

MAPK3 - ERK1:

MAPK4 (Mitogen-Activated Protein Kinase 4):

MAPK6 (Mitogen-Activated Protein Kinase 6):

MAPK7 (Mitogen-Activated Protein Kinase 7):

MAPK8 - JNK:

MAPK9 - JNK2:

MAP2K

MAP2K1 - MEK1:

MAP2K2 - MEK2:

MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3):

MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4):

MAP2K5 (Mitogen-Activated Protein Kinase Kinase 5):

MAP2K6 (Mitogen-Activated Protein Kinase Kinase 6):

MAP2K7 (Mitogen-Activated Protein Kinase Kinase 7):

MAP3K

MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1):

MAP3K11 (Mitogen-Activated Protein Kinase Kinase Kinase 11):

MAP3K12 (Mitogen-Activated Protein Kinase Kinase Kinase 12):

MAP3K2 (Mitogen-Activated Protein Kinase Kinase Kinase 2):

MAP3K3 (Mitogen-Activated Protein Kinase Kinase Kinase 3):

MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4):

MAP3K5 - ASK1:

ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):

BRAF (B-Raf proto-oncogene, serine/threonine kinase):

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

RAF

ARAF (V-Raf Murine Sarcoma 3611 Viral Oncogene Homolog):

BRAF (B-Raf proto-oncogene, serine/threonine kinase):

RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1):

RAS

NRAS - GTPase NRas:

HRAS (HRas proto-oncogene, GTPase):

Activators

CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)):

PAK1 (P21-Activated Kinase 1):

GCK (Glucokinase (Hexokinase 4)):

NRAS - GTPase NRas:

MAP4K3 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3):

PAK2 (P21-Activated Kinase 2):

HRAS (HRas proto-oncogene, GTPase):

Targets

ATF2 (Activating Transcription Factor 2):

BCL2 - Bcl-2:

BAD (BCL2-Associated Agonist of Cell Death):

BTG2 (BTG Family, Member 2):

CANX - Calnexin:

CASP9 - Caspase 9:

CDT1 (Chromatin Licensing and DNA Replication Factor 1):

CTTN - Cortactin:

DAPK1 - DAP Kinase 1:

ELK1 (ELK1, Member of ETS Oncogene Family):

EIF4EBP1 - eIF4EBP1:

GJA1 - Connexin 43/GJA1:

HSPB1 - HSP27:

HSF4 (Heat Shock Transcription Factor 4):

MCL1 - MCL-1:

JUN - C-JUN:

MKNK1 (MAP Kinase Interacting serine/threonine Kinase 1):

MKNK2 (MAP Kinase Interacting serine/threonine Kinase 2):

MAPT (Microtubule-Associated Protein tau):

MAPKAPK2 - MAPKAP Kinase 2:

MAPKAPK3 - MAPKAP Kinase 3:

MAPKAPK5 - MAPKAP Kinase 5:

PXN - Paxillin:

PPARG (Peroxisome Proliferator-Activated Receptor gamma):

RGS1 (Regulator of G-Protein Signaling 1):

RPS6KA1 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 1):

RPS6KA2 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 2):

RPS6KA3 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 3):

RPS6KA5 - MSK1:

RPS6KA6 (Ribosomal Protein S6 Kinase, 90kDa, Polypeptide 6):

SGK1 (serum/glucocorticoid Regulated Kinase 1):

SIRT1 (Sirtuin 1):

Sorbs3 - Vinexin:

SPZ1 (Spermatogenic Leucine Zipper 1):

STMN1 - Stathmin 1:

TP53 - p53:

YAP1 (Yes-Associated Protein 1):

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