puzzling protein

Helene Z. Hill, Ph.D. (hill@umdnj.edu)
Thu, 13 May 1999 15:40:46 -0400

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I hope that one of you out there can figure this one out. Here are the =
facts:
1. Serum-free conditioned medium from cultured melanoma cells rescues =
irradiated and chemotherapy-treated cells from death (colony-forming =
ability). It was concentrated and separated by preparative zonal =
electrophoresis (PZE).
2. Neutralizing antiserum (As50) was obtained using activity fractions =
from PZE. On western, the antiserum reacts with 2 proteins of about 40 =
kD in the fractions that have activity in the bioassay. I call the 2 =
proteins upper and lower.=20
3. On MALDI-MS, lower could not be identified and upper appeared to be =
actin but we now know it is contaminated with actin.
4. Upper and lower were excised from coomassie-stained prep gels, =
electroeluted, concentrated and treated with BioBeads to get rid of =
remaining SDS and added PBS (no Ca or Mg). Added anti-Actin (Sigma) at =
1/400 to upper and incubated at 4 deg over the weekend. Centrifuged 30 =
min in microfuge. SDS-PAGE and western showed that pptn was incomplete. =
Upper SN contains upper protein, actin and actin-antibody complex. =
Upper SN, lower and Sigma actin were run on HPLC in 0.1% THF and =
acetonitrile 0-60% at 1 ml/min. Actin elutes at 7-8 minutes. There =
were 3 bands for upper SN, 5-7, 43-44 and 64-66 minutes. The last was =
intensely blue. There were 3 bands for lower, 2 at 5-7 min which I =
pooled and one at 61-63 min which was intensely blue. We assumed that =
the proteins we were purifying would be where the blue was. The peak =
samples were concentrated by speed-vac, resuspended in 0.0625M tris pH =
6.8 and 20% of each (10% of the blue fractions since these were the =
biggest peaks) was run on SDS-PAGE for westerns along with actin. Actin =
ran at about 40 kD and was the only lane that reacted with actin Ab. =
Upper fractions 5-7 and 43-44 had strong reactions with As50 but the MW =
of both was ~57 kD (remember it started at ~40!). Lower fractions 5-7 =
ran funny but was slaunchwise between 40 and 57 kD, a repeat ran at 57 =
kD. The blue fractions did not react with either antibody. =20
5. So where did the actin go in the HPLC? =20
How come proteins that were about 40 kD became 57 kD after HPLC? =20
Why do the fractions that contain the coomassie stain appear to be =
empty of protein? =20
Did the HPLC reagents strip the dye from the proteins?
Can anyone tell me a better way to get the actin out of upper?
Does anyone know where to expect the immunoglobin or the complex to =
come off in the HPLC?

You all have been wonderfully helpful before. I have learned a lot from =
your e-mail conversations with each other. I am learning all of this =
the hard way and these latest results really have me baffled. Any help =
I can get would be greatly appreciated. =20

Lanie Hill

Helene Z. Hill, Ph.D.
Professor of Radiology
NJ Medical School
Newark, NJ 07103-2714
Tel:973-972-3421
Fax:973-972-5592

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I hope that one of you out there can figure this one = out.  Here are the facts:
1. Serum-free conditioned medium from cultured = melanoma cells=20 rescues irradiated and chemotherapy-treated cells from death = (colony-forming=20 ability).  It was concentrated and separated by preparative zonal=20 electrophoresis (PZE).
2. Neutralizing antiserum (As50) was obtained using = activity=20 fractions from PZE.  On western, the antiserum reacts with 2 = proteins of=20 about 40 kD in the fractions that have activity in the bioassay.  I = call=20 the 2 proteins upper and lower. 
3. On MALDI-MS, lower could not be identified and = upper=20 appeared to be actin but we now know it is contaminated with = actin.
4. Upper and lower were excised from = coomassie-stained prep=20 gels, electroeluted, concentrated and treated with BioBeads to get = rid of=20 remaining SDS and added PBS (no Ca or Mg).  Added anti-Actin = (Sigma) at=20 1/400 to upper and incubated at 4 deg over the weekend.  = Centrifuged 30 min=20 in microfuge.  SDS-PAGE and western showed that pptn was = incomplete. =20 Upper SN contains upper protein, actin and actin-antibody complex.  = Upper=20 SN, lower and Sigma actin were run on HPLC in 0.1% THF and acetonitrile = 0-60% at=20 1 ml/min.  Actin elutes at 7-8 minutes.  There were 3 bands = for upper=20 SN, 5-7, 43-44 and 64-66 minutes.  The last was intensely = blue.  There=20 were 3 bands for lower, 2 at 5-7 min which I pooled and one at 61-63 min = which=20 was intensely blue.  We assumed that the proteins we were purifying = would=20 be where the blue was. The peak samples were concentrated by speed-vac,=20 resuspended in 0.0625M tris pH 6.8 and 20% of each (10% of the blue = fractions=20 since these were the biggest peaks) was run on SDS-PAGE for westerns = along with=20 actin.  Actin ran at about 40 kD and was the only lane that reacted = with=20 actin Ab.  Upper fractions 5-7 and 43-44 had strong reactions with = As50 but=20 the MW of both was ~57 kD (remember it started at ~40!).  Lower = fractions=20 5-7 ran funny but was slaunchwise between 40 and 57 kD, a repeat ran at = 57=20 kD.  The blue fractions did not react with either antibody. =20
5. So where did the actin go in the HPLC?  =
    How come proteins that were about = 40 kD=20 became 57 kD after HPLC? 
    Why do the fractions that contain = the=20 coomassie stain appear to be empty of protein? 
    Did the HPLC reagents strip the = dye from=20 the proteins?
    Can anyone tell me a better way = to get the=20 actin out of upper?
    Does anyone know where to expect = the=20 immunoglobin or the complex to come off in the HPLC?
 
You all have been wonderfully helpful before.  = I have=20 learned a lot from your e-mail conversations with each other.  I am = learning all of this the hard way and these latest results really have = me=20 baffled.  Any help I can get would be greatly appreciated. =20
 
Lanie Hill
 
Helene Z. Hill, Ph.D.
Professor of = Radiology
NJ Medical=20 School
Newark, NJ=20 07103-2714
Tel:973-972-3421
Fax:973-972-5592
 
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