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			PubMed Journals: Mol Cell Proteomics

  Source:		PMID: 16195223


    		Mol Cell Proteomics. 2006 Jan;5(1):97-113.
     		Epub 2005 Sep 29.

			Hyperphosphorylation of JNK-interacting
			protein 1, a protein associated with
			Alzheimer disease.

			D'Ambrosio C(1), Arena S, Fulcoli G, Scheinfeld
			MH, Zhou D, D'Adamio L, Scaloni A.

			Author Information
			(1) Proteomics and Mass Spectrometry Laboratory,
			ISPAAM, National Research Council, 80147
			Naples, Italy.

			The c-Jun N-terminal kinase (JNK) group of
			mitogen-activated protein (MAP) kinases
			are activated by pleiotropic signals including
			environmental stresses, growth factors,
			and hormones. JNK-interacting protein 1
			(JIP1) is a scaffold protein that assembles
			and facilitates the activation of the mixed
			lineage kinase-dependent JNK module and
			also establishes an interaction with beta-amyloid
			precursor protein that has been partially
			characterized. Here we show that, similarly
			to other proteins involved in various neurological
			diseases, JIP1 becomes hyperphosphorylated
			following activation of stress-activated
			and MAP kinases. By immobilized metal affinity
			chromatography and a combined microcapillary
			LC/MALDI-TOF/ESI-ion trap mass spectrometry approach, we
			identified 35 sites of mitotic phosphorylation
			within JIP1, among which eight were present
			within (Ser/Thr)-Pro sequence. This motif
			is modified by various kinases in aggregates
			of the microtubule-associated protein tau,
			which generates typical intraneuronal lesions
			occurring in Alzheimer disease. Most of
			the post-translational modifications found
			were located within the JNK, MAP kinase
			kinase, and RAC-alpha Ser/Thr protein kinase
			binding regions; no modifications occurred
			in protein Src homology 3 and phosphotyrosine
			interaction domains, which are essential
			for binding to kinesin, beta-amyloid precursor
			protein, and MAP kinase kinase kinase. Protein
			phosphorylation is known to affect stability
			and protein-protein interactions. Thus,
			the findings that JIP1 is extensively phosphorylated
			after activation of stress-activated and
			MAP kinases indicate that these signaling
			pathways might modulate JIP1 signaling by
			regulating its stability and association
			with some, but not all, interacting proteins.

			DOI: 10.1074/mcp.M500226-MCP200 PMID: 16195223
			[Indexed for MEDLINE]

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