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GCK (human)

Overview GCK Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with RAB8A. Highly expressed in germinal center but not mantle zone B-cells. Also expressed in lung, brain and placenta and at lower levels in other tissues examined. The tumor necrosis factor (TNF), as well as endotoxins and proinflammatory stimuli such as polyinosine- polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Note: This description may include information from UniProtKB. Protein type: Protein kinase, Ser/Thr (non-receptor); Protein kinase, STE; Motility/polarity/chemotaxis; EC 2.7.11.1; Kinase, protein; STE group; STE20 family; KHS subfamily Cellular Component: Golgi membrane; basolateral plasma membrane Molecular Function: protein serine/threonine kinase activity; protein binding; mitogen-activated protein kinase kinase kinase binding; ATP binding; small GTPase regulator activity Biological Process: vesicle targeting; protein kinase cascade; positive regulation of JNK cascade; response to stress; innate immune response; JNK cascade; immune response; protein amino acid phosphorylation; activation of JNK activity Reference #:  Q12851 (UniProtKB) Alt. Names/Synonyms: B lymphocyte serine/threonine protein kinase; B lymphocyte serine/threonine-protein kinase; BL44; GC kinase; GCK; Germinal center kinase; germinal centre kinase (GC kinase); M4K2; MAP4K2; MAPK/ERK kinase kinase kinase 2; MEK kinase kinase 2; MEKKK 2; Mitogen-activated protein kinase kinase kinase kinase 2; Rab8 interacting protein; Rab8-interacting protein; RAB8IP Gene Symbols: MAP4K2 Molecular weight: 91,556 Da Basal Isoelectric point: 5.91  Predict pI for various phosphorylation states CST Pathways:  SAPK/JNK Signaling Cascades Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below GCK

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	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		S8-p	MALLRDVsLQDPRDR
0	3		Y27-p	QRVGAGTyGDVYkAR
0	1		K32-u	GTyGDVYkARDTVTS
0	3		S170-p	ASVAKRRsFIGTPYW
0	1		S227-p	MRALMLMsKSSFQPP
0	1		S298-p	DPHLGTPsPEDCELE
0	1		T306-p	PEDCELEtyDMFPDT
0	4		Y307-p	EDCELEtyDMFPDTI
0	8		T326-p	QHGPAERtPsEIQFH
0	67		S328-p	GPAERtPsEIQFHQV
0	10		S394-p	SEFQELDsPDDTMGT
0	3		T574-p	QVPLSIPtNRLtQRI
0	4		T578-p	SIPtNRLtQRIIPRR
0	1		T819-p	ILTGHQStY______

	mouse
S8	MALLRDVSLQDPRDR
Y27	QRVGAGTYGDVYKAR
K32	GTYGDVYKARDTVTS
S170	ASVAKRRSFIGTPYW
S227	MRALMLMSKSSFQPP
S298	DPHLGTLSPEDSELE
T306	PEDSELETHDMFPDT
H307	EDSELETHDMFPDTI
T326-p	HHGPAERtPsEIQFH
S328-p	GPAERtPsEIQFHQV
S394-p	LELQELDsPDDAIGT
T575	QAPLSIPTNRITQRI
T579	SIPTNRITQRIIPRR
S820	ILTGHQSSY______

	rat
S8	MALLRDVSLQDPRDR
Y27-p	QRVGAGTyGDVYKAR
K32	GTyGDVYKARDTVTS
S170	ASVAKRRSFIGTPYW
S227	MRALMLMSKSSFQPP
S298	DPHLGTLSPEDSELE
T306	PEDSELETHDMFPDT
H307	EDSELETHDMFPDTI
T326	HHGPAERTPSEIQFH
S328	GPAERTPSEIQFHQV
S394	IELQELDSPDDAIGT
T575	QAPLSIPTNRITQRI
T579	SIPTNRITQRIIPRR
S820	ILTGHQSSY______

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