*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 11606564


    		J Biol Chem. 2002 Jan 11;277(2):1531-7.
     		Epub 2001 Oct 17.

			Phosphorylation of Ser307 in
			insulin receptor substrate-1 blocks interactions
			with the insulin receptor and inhibits insulin
			action.

			Aguirre V(1), Werner ED, Giraud J, Lee YH,
			Shoelson SE, White MF.

			Author Information
			(1) Howard Hughes Medical Institute,
			Joslin Diabetes Center, Harvard Medical School,
			Boston, Massachusetts 02215, USA.

			Serine phosphorylation of
			insulin receptor substrate-1 (IRS-1) inhibits
			insulin signal transduction in a variety
			of cell backgrounds, which might contribute
			to peripheral insulin resistance. However,
			because of the large number of potential
			phosphorylation sites, the mechanism of
			inhibition has been difficult to determine. One
			serine residue located near the
			phosphotyrosine-binding (PTB) domain in
			IRS-1 (Ser(307) in rat IRS-1 or Ser(312)
			in human IRS-1) is phosphorylated via several
			mechanisms, including insulin-stimulated
			kinases or stress-activated kinases like
			JNK1. During a yeast tri-hybrid assay,
			phosphorylation of Ser(307) by JNK1 disrupted
			the interaction between the catalytic domain
			of the insulin receptor and the PTB domain
			of IRS-1. In 32D myeloid progenitor cells,
			phosphorylation of Ser(307) inhibited insulin
			stimulation of the phosphatidylinositol
			3-kinase and MAPK cascades. These results
			suggest that inhibition of PTB domain function
			in IRS-1 by phosphorylation of Ser(307)
			(Ser(312) in human IRS-1) might be a general
			mechanism to regulate insulin signaling.

			DOI: 10.1074/jbc.M101521200 PMID: 11606564
			[Indexed for MEDLINE]

     			                         Tweet       Print