The structure and function of p55PIK reveal a new regulatory subunit for phosphatidylinositol 3-kinase.
Phosphatidylinositol 3-kinase (PI-3 kinase) is implicated in the regulation of diverse cellular processes, including insulin-stimulated glucose transport. PI-3 kinase is composed of a 110-kDa catalytic subunit and an 85-kDa regulatory subunit. Here, we describe p55PIK, a new regulatory subunit that was isolated by screening expression libraries with tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1). p55PIK is composed of a unique 30-residue NH2 terminus followed by a proline-rich motif and two Src homology 2 (SH2) domains with significant sequence identify to those in p85. p55PIK mRNA is expressed early during development, remains abundant in adult mouse brain and testis tissue, and is detectable in adult adipocytes and heart and kidney tissues. p55PIK forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation. Moreover, the activated insulin receptor phosphorylates p55PIK in Sf9 cells, and insulin stimulates p55PIK phosphorylation in CHOIR/p55PIK cells. The unique features of p55PIK suggest that it is important in receptor signaling.
Pons
S
S
Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Asano
T
T
Glasheen
E
E
Miralpeix
M
M
Zhang
Y
Y
Fisher
T L
TL
Myers
M G
MG
Sun
X J
XJ
White
M F
MF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005314:Embryonic and Fetal Development; D015971:Gene Expression Regulation, Enzymologic; D015723:Gene Library; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011972:Receptor, Insulin / Q000378:metabolism; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011972:Receptor, Insulin; D016392:Proto-Oncogene Proteins pp60(c-src)